Timeline human development

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Introduction

This page is organised to show a week by week human timeline of development features and approximate timing of key events with more detailed information about specific events in different systems. For a less detailed timeline see week by week.

From a single cell to a newborn infant in 9 months.
Early zygote.jpg Newborn.jpg Human development timeline graph 01.jpg
Embryonic Development
  • "Weeks" refer to embryonic development from fertilization.
    • Clinical weeks (shown in brackets) or Gestational Age GA) is from the first day of the Last Menstrual Period (LMP).
  • "Stages" refer to the Carnegie stages of development.
  • "Timing" refers to days from fertilization or post conception age (PC), not the clinical or gestational age (GA) calculated from LMP (add 2 weeks).
  • Dates and staging are also "ideal", and there is significant biological variability in the general timing of events.
  • Week 1 to Week 8 (GA 10)are considered the embryonic period of development.
  • Week 9 to week 37 (GA 11-39) or birth are considered the fetal period of development.
  • First month (4 weeks) after birth is the neonatal period of development.


Each developmental feature is linked to online content with more detailed information and resources such as images and movies. The superscript numbers are the original source references. There are similar "timelines" for other species shown below.


Timeline Links: human timeline | mouse timeline | mouse detailed timeline | chicken timeline | rat timeline | zebrafish timeline | Medaka | comparative | Category:Timeline
Human Trimesters - Systems  
Period: first trimester timeline | second trimester timeline | third trimester timeline

Systems: bone timeline | eye neural crest timeline | heart abnormality timeline | hearing timeline | hearing EAM timeline | muscle timeline | ovary timeline | pelvis timeline | placental villi timeline | shoulder timeline | smell timeline | spleen timeline | ventricular timeline

Historic  
upper limb ossification timeline | lower limb ossification timeline | 1932 Guinea pig day 11-21 | 1933 Guinea pig day 21-35
Embryology History: 1600-1699 | 1700-1799 | 1800-1899 | 1900-1909 | 1910-1919 | 1920-1929 | 1930-1939 | 1940-1949 | 1950-1959 | 1960-1969 | 1970-1979 | 1980-1989 | 1990-1999 | Historic Papers | Embryologists

First Trimester

Week: 1 2 3 4 5 6 7 8
Carnegie stage: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23


First Trimester Timeline 
Links: human timeline | first trimester timeline | second trimester timeline | third trimester timeline
Gestational Day GA
Stage
Event
1
Menstrual Phase
Menstrual cycle.png

menstrual cycle changes: uterus endometrium (loss), ovary (follicle development)

2
  Human- menstrual uterine endometrium.jpg
3
 
4
   
5
Proliferative Phase Smear- early proliferative.jpgOva41he.jpg menstrual cycle changes: uterus endometrium (proliferation), ovary (Follicle Development)
6
7
   
8
Proliferative Phase
9
  Smear- mid-proliferative.jpg Human- mid-proliferative uterine endometrium.jpg Ovary10x.jpg Ova20he.jpg menstrual cycle - Mid proliferative
10
   
11
   
12
   
13
  Smear- late-proliferative.jpg Human- late proliferative uterine endometrium.jpg Menstrual cycle.png menstrual cycle - Late Proliferative
14
ovulation

Capacitation

Human ovulation 06.jpg Human oocyte.jpg Follicle 001 icon.jpg
Fertilization Day
Stage
Event
1
Secretory Phase

Stage 1

Early zygote.jpg Stage1 size with ruler.jpgSmear- secretory.jpg Human- secretory uterine endometrium.jpg fertilization, zygote, Secretory Phase
2
Stage 2 Stage2.jpg Week1 001 icon.jpg morula, Blastula
3
  Human-blastocyst-day-3-6-icon.jpg blastocyst
4
Stage 3 CSt3.jpg blastocyst Hatching (zona pellucida lost)
5
  Smear- late secretory.jpg Human- late secretory uterine endometrium.jpg Late Secretory, blastocyst (free floating)
6
Stage 4 Adplantation
7
Stage 5 Week2 001 icon.jpgStage5 bf11L.jpg
8
Week2 001 icon.jpg implantation
9
   
10
   
11
   
12
   
13
Stage 6 Stage6 bf03.jpgChorion 001 icon.jpg Chorionic Cavity
14
   
Day
Stage
Event
15
16
Stage 7 Stage7-bf1.jpg Stage7-sem2.jpg Stage7.jpg gastrulation, ectoderm, mesoderm, endoderm
17
   
18
Stage 8 Stage8 human.jpg Neuralplate 001 icon.jpg neural neurogenesis, neural groove and folds are first seen
19
 
Stage8 SEM1.jpg
20
Stage 9 Stage9 bf2c.jpg Stage9 sem1b.jpg Musculoskeletal somitogenesis, first somites form and continue to be added in sequence caudally (1 - 3 somite pairs).

neural the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open

Neural Crest mesencephalic neural crest is visible[1]

21
  heart cardiogenesis, week 3 begins as paired heart tubes.
Day
Stage
Event
22
Stage 10 Stage10 bf2c.jpg Stage10 sem10c.jpg Neuraltube 001 icon.jpg

Neural Crest differentiation at spinal cord level from day 22 until day 26

neural folds begin to fuse near the junction between brain and spinal cord, when Neural Crest cells are arising mainly from the neural ectoderm

Neural Crest trigeminal, facial, and postotic ganglia components visible[1]

Neural Crest migration of vagal level neural crest cells begins (7-10 somite stage)

neural rostral neural tube forms 3 primary brain vesicles (week 4)

respiratory Week 4 - laryngotracheal groove forms on floor foregut.

23
  heart begins to beat in Humans by day 22-23, first functioning embryonic organ formed.
24
Stage 11 Stage11 bf2c.jpg

thyroid - thyroid median endodermal thickening in the floor of pharynx

neural rostral (or cephalic) neuropore closes within a few hours; closure is bidirectional, it takes place from the dorsal and terminal lips and may occur in two areas simultaneously. The two lips, however, behave differently.

ventricular Optic ventricle appears and the neural groove/tube space is initially filled with amniotic fluid.[2]

25
Stage 12 Stage12 bf2b.jpg Stage12 sem1.jpg

pituitary Week 4 hypophysial pouch, Rathke's pouch, diverticulum from roof

liver septum transversum forming liver stroma and hepatic diverticulum forming hepatic trabeculae[3]

neural caudal neuropore takes a day to close (closure is approximately at future somitic pair 31/sacral vertebra 2)

neural secondary neurulation begins

ventricular onset of the ventricular system and separates the ependymal from the amniotic fluid.[2]

neural crest cardiac crest, neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there the truncus arteriosus[1]

neural crest vagal neural crest enter the foregut (20-25 somite stage)

26
   
27
   
28
Stage 13 Stage13 bf1c.jpg Stage13 sem1c.jpg neural the neural tube is normally completely closed, ventricular system now separated from amniotic fluid. Neural crest at spinal level is segregating, and spinal ganglia are in series with the somites. Spinal cord ventral roots beginning to develop.[4]

telencephalon cavity appears

Neural - Vascular Development - hindbrain is supplied by two parallel neural arteries (or channels) that obtain their blood supply from carotid-vertebrobasilar anastomoses given by the pharyngeal arch arteries; trigeminal artery, the otic artery, hypoglossal artery, and the proatlantal artery.[5]

liver epithelial cord proliferation enmeshing stromal capillaries[3]

smell Crest comes from the nasal plates[6]

integumentary 4 weeks - simple ectoderm epithelium over mesenchyme

integumentary 1-3 months ectoderm- germinative (basal) cell repeated division of generates stratified epithelium; mesoderm- differentiates into connective tissue and blood vessels

vision Optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lens placode.[7]

Diaphragm - pleuroperitoneal fold (PPF) first discernible in human embryos (CRL 6mm).[8]

29
pituitary Week 5 elongation, contacts infundibulum, diverticulum of diencephalon

heart Week 5 septation starts, atrial and ventricular

respiratory Week 5 left and right lung buds push into the pericardioperitoneal canals (primordia of pleural cavity)

Respiratory Week 5 to 17 lung histology - pseudoglandular

hearing Week 5 cochlear part of otic vesicle elongates (humans 2.5 turns)

30
   
31
   
32
Stage 14 Stage14 bf2l.jpg Stage14 sem1c.jpg Placodes sensory placodes, lens pit, otocyst, nasal placode, primary/secondary vesicles, fourth ventricle of brain

somite continued segmentation of paraxial mesoderm (somite pairs), heart prominence

head 1st, 2nd and 3rd pharyngeal arch, forebrain, site of lens placode, site of otic placode, stomodeum

Body - heart, liver, umbilical cord, mesonephric ridge visible externally as bulges.

limb upper and lower limb buds growing.

Abdominal Wall mesoderm of the primary body wall coalesced in the ventral midline to create the abdominal cavity.[9]

neural first appearance of the future cerebral hemispheres. Cerebellar plate differentiated to an intermediate layer, and future rhombic lip identifiable[10]

Neural - Vascular Development - basilar artery forms from the consolidation of the neural arteries.[5]

ventricular Subarachnoid space initially as irregular spaces on the ventral surface of the spinal cord.[11]

liver hepatic gland and its vascular channels enlarge, hematopoietic function appears[3]

vision lens placode is indented by the lens pit.[7]

33
Stage 15 Stage15 bf1c.jpg

neural cranial nerves (except olfactory and optic) are identifiable in more advanced embryos[12]

Neural - Vascular Development - vertebral arteries form from transverse anastomoses between cervical intersegmental arteries, beginning with the proatlantal artery and proceeding downward to the 6th intersegmental artery,[5]

vision lens pit is closed. The lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface.[7]

34
 
35
  vision 35 to 37 days retinal pigment present
36
pituitary Week 6 - connecting stalk between pouch and oral cavity degenerates

parathyroid Week 6 - diverticulum elongate, hollow then solid, dorsal cell proliferation

thymus Week 6 - diverticulum elongate, hollow then solid, ventral cell proliferation

adrenal Week 6 - fetal cortex forms from mesothelium adjacent to dorsal mesentery, medulla neural crest cells from adjacent sympathetic ganglia

respiratory Week 6 - descent of heart and lungs into thorax. Pleuroperitoneal foramen closes

tongue Week 6 - gustatory papilla, caudal midline near the foramen caecum (week 6 to 7 - nerve fibers approach the lingual epithelium)

37
Stage 16 Stage16 bf1c.jpg Neural first parasympathetic ganglia, submandibular and ciliary, are identifiable[13]

Neural - Vascular Development - development of the middle cerebral artery is first identified as small buds originating proximal to the anterior cerebral artery on the anterior division of the primitive internal carotid artery.[5]

limb upper limb bud nerves median nerve, radial nerve and ulnar nerve entered into hand plate, myoblasts spindle shaped and oriented parallel to limb bud axis.

Abdominal Wall muscle cell migration about 25% of the hemicircumference of the abdominal cavity, the lateral plate mesoderm has become more condensed and thicker in the area around the myoblasts.[9]

heart outflow tract elliptical configuration with four cushions, the two larger fusing at this stage. Semilunar valve leaflets form at the downstream end of the cushions

head lip and palate components of the upper lip, medial nasal prominence and maxillary process present, median palatine process appears.

Eyelid prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it.[7]

38
   
39
   
40
   
41
Stage 17 Stage17 bf1c.jpg
  • neural
    • telencephalon areas of the future archicortex, paleocortex, and neocortex, visible. Beginning of future choroid plexus[14]
    • ventricular primordium of the epidural space appears first on the ventral part of the vertebral canal and develops rostro-caudally[15]
  • smell olfactory nerve fibres enter the brain[6]
  • Eyelid sulcus (groove) above and below eye deepen and eyelid folds develop (below first and then above)[7]
  • Diaphragm - pleuroperitoneal fold (PPF) no longer separated from the diaphragm (CRL 14mm)[8]
  • Abdominal Wall muscle cells now migrated approximately 50% of the distance to the ventral midline, inner and outer layers were not discernible yet.[9]
42
  heart separation of common cardiac outflow (aortic arch and pulmonary aorta)
Day
Stage
Event
43
pancreas Week 7 to 20 pancreatic hormones secretion increases, small amount maternal insulin

respiratory Week 7 - enlargement of liver stops descent of heart and lungs

44
Stage 18 Stage18 bf1c.jpg

limb bone forms by endochondrial ossification and throughout embryo replacement of cartilage with bone (week 5-12).

neural smell vomeronasal fibres and nervus terminalis[6]

liverobturation due to epithelial proliferation, bile ducts became reorganized, continuity between liver cells and gut[3]

ventricular duramater appears and spaces surround the circumference of the spinal cord, which coalesce and contain many blood vessels.[15]

Female uterus opening of the paramesonephric (Müllerian) duct to the coelomic cavity formed as an invagination of the coelomic epithelium[16]

Abdominal Wall separation of the myoblasts into distinct inner and outer layers, with unidirectional orientation. Abdominal wall thicker in the region where secondary structures were forming compared with the primary body wall region, dorsally outermost layer of connective tissue approximately half of this thickness.[9]

45
   

liver (stage 18 to 23) biliary ductules developed in periportal connective tissue

produces ductal plates that receive biliary capillaries[3]

46
   
47
   
48
Stage 19 Stage19 bf1c.jpg
  • vision - (stage 19 -22) eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19.[7]
  • cardiovascular
  • Respiratory - first generation of subsegmental bronchi now complete, see bronchial tree reconstruction[20] (plates 3 and 4).
  • gastrointestinal tract - anal membrane defined.
  • renal - Cloacal membrane ruptures from urinary pressure at stage 18 or stage 19,
  • genital
    • testis - Rete testis develops from the seminiferous cords at stages 19–23, and tunica albuginea forms.[21].
    • ovary - Rete ovarii cords are developing.[22]
    • uterus Müllerian duct grows independently from the invagination of the coelomic epithelium during stages 19-23[16]
  • musculoskeletal
    • Sternum right and left sternal bars are present.[23] (figs. 7-17 and 7-22)
    • Abdominal Wall segregation of the myoblasts into four distinct muscle groups with unidirectional orientation of myoblasts. Myoblast migrated over half of the distance to the ventral midline, abdominal wall thickest where the muscles migrated and the outermost layer of connective tissue comprises approximately half of the total thickness of the abdominal wall. Rectus muscle completely separated after migrating over half the distance to the midline.[9]
  • neural
    • rhombencephalon migration for olivary and arcuate nuclei begins.
    • choroid plexus of the fourth ventricle present.
    • stria medullaris thalami reaches the habenular nuclei.
    • habenular commissure begins to develop.
    • accessory olivary nucleus appears[24]
    • Neural - Vascular Development - middle cerebral artery becomes more prominent, the plexi fuse into a single artery and further branches pierce the cerebral hemisphere.[5]
49
   
50
Stage 20 Stage20 bf1c.jpg

Head scalp vascular plexus visible

limb upper limbs begin to rotate ventrally

neural amygdaloid body has at least four individual nuclei[24]

oculomotor nerve shows a dorsolateral and a ventromedial portion

rhombic lip (rhombencephalon) formation of the cerebellum (intermediate layer) and of the cochlear nuclei

cerebellum cell layer (future Purkinje cells) develops

choroid plexuses of the fourth and lateral ventricles

Eyelid the inner canthus is established.[7]

51
  gastrointestinal tract anal membrane perforates
52
Stage 21 Stage21 bf1c.jpg

neural cortical plate appears in the area of future insula[25]

Neural - Vascular Development - formation of the anterior communicating artery.[5]

limb upper and lower limbs rotate

Intraembryonic Coelom pericardioperitoneal canals close

Abdominal Wall Myoblasts have reached the ventral midline and myotubes were present and oriented uniformly within all muscle groups. The rectus abdominis formed distinct bundles of muscle. Connective tissue layers comprised the majority of the thickness of the abdominal wall, outermost layer of connective tissue accounted for the majority of this thickness.[9]

53
   
54
Stage 22 Stage22 bf1c.jpg neural neocortical fibres project to epithalamus, to dorsal thalamus, and to mesencephalon[25]

limb fingers and toes lengthen

smell Stage 22 to early fetal period - migratory streams of neurons from the subventricular zone of the olfactory bulb towards the future claustrum[6]

Uterus Vagina fused duct (uterovaginal canal) bifurcated at the caudal portion at Carnegie stages 22 and 23[16]

55
Genital 8 Weeks Testis - mesenchyme, interstitial cells (of Leydig) secrete testosterone, androstenedione

Genital 8 to 12 Weeks - hCG stimulates testosterone production

Tongue Week 8 - nerves penetrate epitheilai basal lamina and synapse with undifferentiated, elongated, epithelial cells (taste bud progenitor cell)[26]

56
Stage 23 Stage23 bf1c.jpg Stage 23 defines the end of the embryonic (organogenesis) period

Mesoderm heart prominence, ossification continues

Head nose, eye, external acoustic meatus, eyelids, external ears, rounded head

Body - straightening of trunk, umbilical cord, intestines herniated at umbilicus

limb upper limbs longer and bent at elbow, hands and feet turned inward, foot with separated digits, wrist, hand with separated digits

Extraembryonic Coelom chorionic cavity is now lost by fusion with the expanding amniotic cavity

neural rhombencephalon, pyramidal decussation present, nuclei and tracts similar to those present in the newborn cerebellum present as only a plate connected to midbrain and hindbrain through fibre bundles[27]

Axial Skeleton vertebral column 33 or 34 cartilaginous vertebrae (20-33 mm in total length), vertebral pedicles, articular and transverse processes identifiable (no spinous processes)[28]

Abdominal Wall Rectus muscle forms 2 or 3 distinct layers with myotube orientation uniform in all muscles. The external oblique and internal oblique started to expand in thickness, transversus a thin layer of muscle.[9]

 
Week 8 Stomach Week 8 - Gastrin containing cells in stomach antrum. Somatostatin cells in both the antrum and the fundus.

Genital - Female Development paired paramesonephric (Müllerian) ducts contact each other and are fused into a single tube that separates again and returns to the mesonephric (Wolffian) ducts. The paramesonephric ducts have not yet reached the urogenital sinus.[16]

57-63
Week 9 Beginning of Fetal Development


Historic Embryology
Embryology History George Streeter In 1949 the embryologist George Streeter[29] used the replacement of cartilage within the humerus by bone marrow as an arbitrary definition of the embryo to fetus transition.
"If the onset can be recognized in a given specimen, that specimen is straightway classed as a fetus."


CRL 43 mm, femur length 6 mm

9 weeks CRL 50 mm - genital genitalia in both sexes look identical[30]

uterus - paramesonephric ducts come into apposition with the urorectal septum and begin to fuse

Day
Stage
Event
64
Size comparison embryo-fetus actual.jpg

Gastrointestinal Tract Week 10 intestines in abdomen

Pituitary growth hormone and ACTH detectable

Pancreas Week 10 glucagon (alpha) differentiate first, somatostatin (delta), insulin (beta) cells differentiate, insulin secretion begins

Tongue Week 10 shallow grooves above the taste bud primordium

Stomach Week 10 - Glucagon containing cells in stomach fundus.

Nail Development fingernails appear

outer ear Week 10 - Meatal plug extends in a disc-like fashion, the meatus is boot-shaped with a narrow neck and the sole of the meatal plug spreading widely to form the future tympanic membrane medially. Proximal portion of the neck starts to be resorbed.

inner ear Week 10 - neural-crest-derived melanocytes migrate into the cochlea. They penetrate the basement membrane of the lateral wall epithelium and develop into the intermediate cells of the stria vascularis.[31]

65
   
66
 
67
   
68
 
69
   
70
Week 10 - CRL 55 mm, femur length 9 mm, biparietal diameter 17 mm
Day
Stage
Event

neural - Cerebrum appearance of the first sulcus (week 11-15, GA 13-17 weeks)[32]

71
Size comparison embryo-fetus actual.jpg

Thyroid colloid appearance in thyroid follicles, iodine and thyroid hormone (TH) synthesis

Stomach Week 11 - Serotonin containing cells in both the antrum and the fundus.

72
   
73
 
74
   
75
 
76
   
77
Week 11 - CRL 68 mm, femur length 12 mm, biparietal diameter 20 mm
Systems  
Systems: bone timeline | eye neural crest timeline | heart abnormality timeline | hearing EAM timeline | muscle timeline | ovary timeline | placental villi timeline | shoulder timeline | smell timeline | spleen timeline | ventricular timeline

Second Trimester

(GA Clinical Week 14) Second Trimester

Second Trimester Timeline 
Links: human timeline | first trimester timeline | second trimester timeline | third trimester timeline
Week
Stage
Event
12
Clinical second trimester Fetal head lateral.jpg Week 12 - CRL 85 mm, femur length 15 mm, biparietal diameter 25 mm

Hearing Week 12-16 - Capsule adjacent to membranous labrynth undegoes vacuolization to form a cavity (perilymphatic space) around membranous labrynth and fills with perilymph


Genital male and female external genital differences observable

Respiratory Month 3-6 - lungs appear glandular, end month 6 alveolar cells type 2 appear and begin to secrete surfactant

Tongue Week 12 - first differentiated epithelial cells (Type II and III)

Genital female genital canal (80 days) formed with absorption of the median septum

13
  tongue Week 12 to 13 - maximum synapses between cells and afferent nerve fibers

hearing outer ear Week 13 - Meatal plug disc-like, innermost surface in contact with the primordial malleus, contributes to the formation of the tympanic membrane.  

14
tongue Week 14 to 15 - taste pores develop, mucous

ovary 100 days - primary follicles present

nail toenails appear

Head Development facial skeleton remodelling begins

Hearing - Inner Ear Development Week 14 GA 16 - neural-crest-derived melanocytes, now intermediate cells of the stria vascularis, tightly integrate with Na+ /K+ -ATPase-positive marginal cells, which started to express KCNQ1 in their apical membrane.[31]

15
  Pancreas glucagon detectable in fetal plasma.

spleen Week 15 -alpha-smooth muscle actin (alpha-SMA)-positive reticulum cells scattered around the arterioles.[33]

16
14 cm Fetal size change.jpg Hearing Week 16-24 - Centres of ossification appear in remaining cartilage of otic capsule form petrous portion of temporal bone. Continues to ossify to form mastoid process of temporal bone.

pituitary adenohypophysis fully differentiated

respiratory Week 16 to 25 lung histology - canalicular

Hearing - Outer Ear Development Week 16.5 - External auditory meatus is fully patent throughout its length, lumen is still narrow and curved.

Hearing - Inner Ear Development Week 16 GA 18 - cells in the outer sulcus express KCNJ10 and gap junction proteins GJB2/CX26 and GJB6/CX30, but these are not expressed in the spiral ligament.[31] gap junction cartoon

neural - Cerebrum development of the periinsular sulci (week 16-17, GA 18-19 weeks)[32]


integumentary 4 months - basal cell- proliferation generates folds in basement membrane; neural crest cells- (melanocytes) migrate into epithelium; embryonic connective tissue- differentiates into dermis, a loose ct layer over a dense ct layer. Beneath the dense ct layer is another loose ct layer that will form the subcutaneous layer. Ectoderm contributes to nails, hair follictles and glands. Nails form as thickening of ectoderm epidermis at the tips of fingers and toes. These form germinative cells of nail field. Cords of these cells extend into mesoderm forming epithelial columns. These form hair follocles, sebaceous and sweat glands.

primary follicles begin to form in the ovary and are characterized by an oocyte

glandular urethra forms and skin folds present

17
Brain week 17 histology.jpg Neural - Brain development histology week 17

Cerebellum Magnetic Resonance Imaging (MRI) can study the developing cerebellum from 17 to 18 weeks (GA 19 to 20 weeks).

tooth Week 17 - First papilla of the permanent dentition appear (first molar) immediately behind the second milk molar, milk teeth are well advanced (Fetus 180 mm).

18
Bailey095.jpgtongue Week 18 - substance P detected in dermal papillae, not in taste bud primordia

integumentary vernix caseosa covers skin

spleen Week 18 - alpha-SMA-positive reticulum cells increase in number and began to form a reticular framework. An accumulation of T and B lymphocytes occurred within the framework, and a primitive white pulp was observed around the arterioles.[33]

Hearing - Outer Ear Development week 18 - External auditory meatus is already fully expanded to its complete form.

neural - Cerebrum central sulci and opercularization of the insula (week 18-20, GA 20-22 weeks)[32]

19
  neural week 19 neuronal migration ends and the radial glial cells that aided the migration now become transformed into astrocytes and astrocytic precursors.[34]
20
  pituitary week 20 to 24 growth hormone levels peak, then decline

integumentary lanugo, skin hair

integumentary 5 months - Hair growth initiated at base of cord, lateral outgrowths form associated sebaceous glands; Other cords elongate and coil to form sweat glands; Cords in mammary region branch as they elongate to form mammary glands.

touch pacinian corpuscle begin to develop[35]

21
   
22
  Gray0038.jpg Neural brain cortical sulcation - sylvian fissure, interhemispheric fissure, callosal sulcus, parietooccipital fissure, and hippocampic fissures present[36]

spleen - Week 22 - antigenic diversity of the reticular framework was observed, and T and B lymphocytes were segregated in the framework. T lymphocytes were sorted into the alpha-smooth muscle actin-positive reticular framework, and the periarteriolar lymphoid sheath (PALS) was formed around the arteriole. B lymphocytes aggregated in eccentric portions to the PALS and formed the lymph follicle (LF). The reticular framework of the LF was alpha-SMA-negative. [33]

neural - Cerebrum covering of the posterior insula (week 22-24, GA 24-26 weeks)[32]

23
   
24
  respiratory Week 24 to 40 lung histology - terminal sac

spleen Week 24 - marginal zone appeared in the alpha-smooth muscle actin-positive reticular framework around the white pulp.[33]

tooth Week 24 - Permanent incisors and canines appear.

Earliest potential survival expected if born

ovary follicles can consist of growing oocytes surrounded by several layers of granulosa cells

25
  respiratory end month 6 alveolar cells type 2 appear and begin to secrete surfactant

neural - Cerebrum closure of the laeteral sulcus (Sylvian fissure or lateral fissure) (week 25-26, GA 27-28 weeks)[32]

26
  touch pacinian corpuscle well developed[35]
Systems  
Systems: bone timeline | eye neural crest timeline | heart abnormality timeline | hearing EAM timeline | muscle timeline | ovary timeline | placental villi timeline | shoulder timeline | smell timeline | spleen timeline | ventricular timeline

Third Trimester

Third Trimester Timeline
Links: human timeline | first trimester timeline | second trimester timeline | third trimester timeline
Week
Stage
Event
Clinical third trimester Fetal size change.jpg hearing 3rd Trimester - vibration acoustically of maternal abdominal wall induces startle respone in fetus.
27
 
28
  respiratory Month 7 - respiratory bronchioles proliferate and end in alveolar ducts and sacs
29
 

tooth Week 29 - Permanent premolars (correspond to the milk molars) appear.

30
   

Genital male gonad (testes) descending

31
 
32
  nail fingernails reach digit tip
33
  neural brain cortical sulcation - primary sulci present[36]
34
  neural brain cortical sulcation - insular, cingular, and occipital secondary sulci present[36]
35
   
36
  Frazer006 bw600.jpg Nail Development toenails reach digit tip

Lens Development - lens growth and interocular distance plateaus after 36 weeks of gestation[37]

37
   
38
Birth Newborn.jpg Clinical Week 40

Heart pressure difference closes foramen ovale leaving a fossa ovalis

thyroid TSH levels increase, thyroxine (T3) and T4 levels increase to 24 h, then 5-7 days postnatal decline to normal levels

adrenal - zona glomerulosa, zona fasiculata present

Systems  
Systems: bone timeline | eye neural crest timeline | heart abnormality timeline | hearing EAM timeline | muscle timeline | ovary timeline | placental villi timeline | shoulder timeline | smell timeline | spleen timeline | ventricular timeline

Postnatal

Week
Stage
Event
+1
Normal Newborn Neural Exam Movies  
Normal Newborn Neural Exam Movies

The newborn neuromuscular system can be initially assessed by 6 quick tests (posture, square window, arm recoil, popliteal angle, scarf sign and heel to ear). The following short videos show clinical examination of these assessments and a number of neonatal reflexes.

Later developmental assessment includes behaviour, reflexes (primitive and postural), muscular tone, and motor (gross, fine, co-ordination).

Normal Newborn Neural Exam Movies

Newborn Behaviour
Newborn-normal-behaviour.jpg
 ‎‎Behaviour
Page | Play
Newborn n 02.jpg
 ‎‎Cranial Nerves
Page | Play
Newborn Tone
Newborn n 03.jpg
 ‎‎Resting Posture
Page | Play
Newborn n 04.jpg
‎‎ Tone Upper Limb
Page | Play
Newborn n 05.jpg
‎‎ Arm Traction
Page | Play
Newborn n 06.jpg
 ‎‎Arm Recoil
Page | Play
Newborn n 07.jpg
 ‎‎Scarf Sign
Page | Play
Newborn n 08.jpg
 ‎‎Hand Position
Page | Play
Newborn n 09.jpg
 ‎‎Lower Limb
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 ‎‎Leg Traction
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 ‎‎Leg Recoil
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 ‎‎Popliteal Angle
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 ‎‎Heel to Ear
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 ‎‎Neck Tone
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 ‎‎Head Lag
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 ‎‎Head Control
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Newborn Positions
Newborn n 17.jpg
 ‎‎Prone Position
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 ‎‎Ventral Suspend
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 ‎‎Vertical Suspend
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Newborn Reflexes
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 ‎‎Tendon Reflexes
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 ‎‎Plantar Reflex
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 ‎‎Reflex Suck,Root
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 ‎‎Moro Reflex
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 ‎‎Galant Reflex
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 ‎‎Stepping Reflex
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 ‎‎Grasp Reflex
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Newborn Head
Newborn n 27.jpg
‎‎ Head Shape
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‎‎Head Circumference
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Neural Exam Movies: normal behaviour | cranial nerves | Newborn Tone - resting posture | upper extremity‎ | arm traction | arm recoil | scarf sign | hand position | lower extremity | leg traction‎ | leg recoil‎‎ | popliteal angle‎ | heel to ear | neck tone | head lag‎ | head control | Newborn Positions - prone | ventral suspension | vertical suspension | Newborn Reflexes - deep tendon reflexes | plantar reflex‎ | suck, root | Moro | Galant | stepping‎ | grasp | Newborn Head - head shape and sutures‎ | head circumference‎ | Neonatal Diagnosis


+2
 
+3
 
+4
  vision - eye globe growth plateaus after 42 weeks of gestation[37]  
+5
   
Month
  testis | spermatozoa - about 2 months of age, primordial germ cells (gonocytes) are replaced by adult dark (Ad) and pale (Ap) spermatogonia forming the spermatogonial stem cell (SSC) population that at puberty will commence differentiation into spermatozoa.
Year
 
Year 1
  neural Hearing (6 months to 5 years) thalamocortical afferents to the deeper cortical layers mature and are the first source of input to the auditory cortex[38]


Normal 12 Month Neural Exam Movies  
Normal 12 Month Neural Exam Movies

The following short videos show clinical examination of neural development assessments and a number of reflexes.


12 Months Neural Exam Movies: Shy | Social and Language | Cranial Nerves | Tone - Tone | Reflexes - deep tendon reflexes | plantar reflex‎ | Parachute | Pincer Grasp | Beads in the Cup | Play Ball | Transition in and out of Sitting | Creeping | Stoop and Recover | Motor/Gait - Stand, Walks with Support | Toddler’s Gait | Head Circumference | Neural Exam Movies
Year 2
   
Year 3
  Adrenal - Year 3 zona reticularis present.


Normal 30 Month Neural Exam Movies  
Normal 30 Month Neural Exam Movies

The following short videos show clinical examination of neural development assessments and a number of reflexes.


Neural Exam Movies: Establishing Relationship | Follows Commands | Points to Pictures | Names Pictures | Response to Questions | Pointing to and Naming Body Parts | Motor/Coordination - Using Puppets | Using Measuring Tape | Block Tower | Drawing | Tone | Deep Tendon Reflex | Kicking and Throwing a Ball | Walking, Running
4
   
5
  neural hearing - (5 to 12 years) commissural and association axons in the superficial cortical layers allows communication between subdivisions of the auditory cortex[38]
7-13
  puberty - Female
9-15
puberty - Male

Human Systems

Human Systems: bone timeline | eye neural crest timeline | hearing timeline | heart abnormality timeline | hearing EAM timeline | muscle timeline | ovary timeline | placental villi timeline | shoulder timeline | smell timeline | spleen timeline | ventricular timeline | comparitive

Somite

Human Embryo Somite Number
Week Days Carnegie Stage Somite Number (pairs)
Week 3 19 - 21 9    image 1 - 3
Week 4 22 - 23 10   image 4 - 12
Week 4 23 - 26 11   image 13 - 20
Week 4 26 - 30 12   image 21 - 29
Week 5 28 - 32 13   image 30
Week 5 31 - 35 14   image 30+

Limb

Carnegie stages for limb elements appearance
Skeletal Element Condensed
Mesenchyme
Cartilage Bone
Mouse limb cartilage and bone.jpg Humerus 16 1617 2122
Radius 16 17 2123
Ulna 16 1718 1723
Hand 17 1721 In fetus1and after birth
Femur 17 1718 2223
Patella 20 21 After birth
Tibia 17 1723 2223
Fibula 17 1718 In fetus
Foot 1718 1823 or later in fetus and after birth
   1 Intramembranous ossification at the tips of the distal phalanges of the hand may be in Stage 23.
Reference - O'Rahilly R. Gray DI. and Gardner E. Chondrification in the hands and feet of staged human embryos. (1957) Carnegie Instn. Wash. Publ. 611, Contrib. Embryol., 36:

Neural

Early Neural Timeline
Carnegie Stage Event
8 (about 18 postovulatory days) neural groove and folds are first seen
9 three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open.
10 (two days later) neural folds begin to fuse near the junction between brain and spinal cord, when neural crest cells are arising mainly from the neural ectoderm
11 (about 24 days) the rostral (or cephalic) neuropore closes within a few hours; closure is bidirectional, it takes place from the dorsal and terminal lips and may occur in several areas simultaneously. The two lips, however, behave differently.
12 (about 26 days) The caudal neuropore takes a day to close. The level of final closure is approximately at future somitic pair 31 (corresponds to the level of sacral vertebra 2). Secondary neurulation begins, is the differentiation of the caudal part of the neural tube from the caudal eminence (or end-bud) without the intermediate phase of a neural plate.
13 (4 weeks) the neural tube is normally completely closed.
  Links: neural | Week 3 | Week 4


Neural-development.jpg

Neural timeline overview[39]

Sensorimotor Cortex

Sensorimotor Cortex Timeline
Gestational Age GA weeks Fertilization Age FA weeks Event
18-19 16-17 appearance of the inferior part of the central cerebral sulcus
20-22 18-20 development of the pericentral lateral regions and the beginning of opercularization
24-26 22-24 development of parietal and temporal cortices and the covering of the postcentral insular region
27-28 25-26 maturation of the central cerebral regions
Table data.[40]    Links: sensorimotor cortex | cerebral cortex | second trimester | Sensory System Development

Notochord

Human Notochord Timeline
Carnegie Stage Days Event
7 15 to 17 notochordal process directly rostral to the area of gastrulation.
8 to 10 17 to 23 group of undifferentiated cells that briefly persists. Within the notochordal process, a connection between the amniotic cavity and yolk-sac (neurenteric canal).
8 to 11 17 to 26 notochordal process incorporates entirely into the endoderm, forming the epithelial notochordal plate.
10 to 11 21 to 26 notochordal plate then acquires an “inverted U-shape”, relatively lengthens during these stages and remains intimately associated with the neural tube until stage 12 (26–30 days).
12 26 to 30 notochordal plate detaches completely from the endoderm to form the definitive notochord.
12 to 14 26 to 35 definitive notochord formation then allows the paired dorsal aortae to fuse in-between the notochord and the roof of the gut.
Table data[41]   Links: notochord | timeline | Week 3 | Week 4

Ventricular

Human Embryonic Ventricular Timeline
Week Carnegie Stage Event
Week 4 11 appearance of the optic ventricle. The neural groove/tube space is initially filled with amniotic fluid.
12 closure of the caudal neuropore, onset of the ventricular system and separates the ependymal from the amniotic fluid.
13 cavity of the telencephalon medium is visible.
Week 5 14 cerebral hemispheres and lateral ventricles begin, rhomboid fossa becomes apparent.
15 medial and lateral ventricular eminences cause indentations in the lateral ventricle
Week 6 16 hypothalamic sulcus is evident.
17 - 18 interventricular foramina are becoming relatively smaller, and cellular accumulations indicate the future choroid villi of the fourth and lateral ventricles.
Week 7 18 areae membranaceae rostralis and caudalis are visible in the roof of the fourth ventricle, and the paraphysis is appearing.
19 choroid villi are visible in the fourth ventricle, and a mesencephalic evagination (blindsack) is visible
Week 8 20 choroid villi are visible in the lateral ventricle.
21 olfactory ventricle is visible.
21 - 23 lateral ventricle has become C-shaped (anterior and inferior horns visible). Recesses develop in the third ventricle (optic, infundibular, pineal).
Week: 1 2 3 4 5 6 7 8
Carnegie stage: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Links: ventricular | neural | timeline | Category:Timeline     Table Data Reference[42]

Neural Crest

Human Eye Neural Crest Timeline
Carnegie Stage Event
9 an indication of mesencephalic neural crest
10 trigeminal, facial, and postotic components
11 crest-free zones are soon observable in rhombomere 1, 3, and 5
12 rhombomeres 6 and 7 neural crest migrate to pharyngeal arch 3 and then rostrad to the truncus arteriosus
13 nasal crest and the terminalis-vomeronasal complex are last of the cranial crest to appear
9 to 14 otic vesicle primordium descends
Week: 1 2 3 4 5 6 7 8
Carnegie stage: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Data from a study of 185 serially sectioned staged (Carnegie) human embryos.[1] Links: vision | neural crest | timeline |     Category:Timeline

Hearing

Hearing Timeline
Developmental Time Event
Week 9 Mesenchyme surrounding membranous labryinth (otic capsule) chondrifies.
Week 12-16 Capsule adjacent to membranous labryinth undegoes vacuolization to form a cavity (perilymphatic space) around membranous labrynth and fills with perilymph.
Week 18 ectodermal plug in external auditory meatus breaks down.
Week 16 - 24 Centres of endochondral ossification appear in remaining cartilage of otic capsule form petrous portion of temporal bone. Continues to ossify to form mastoid process of temporal bone.
Week 18 - 22 Organ of corti structural elements develop. (GA 20 - 24 weeks)
26 weeks human brainstem auditory pathway is anatomically formed.
28 weeks AABR can be recorded.
3rd Trimester Vibration acoustically of maternal abdominal wall induces startle response in fetus.
Links: hearing | timeline
Stapedius Timeline
Carnegie
Stage
CRL (mm) Description
13 6 Presumptive stapedial area
14 7 Appearance of the stapedial anlage
16 9 Relationship between the stapedial artery and the stapedial anlage. Appearance of the interhyale
17 12 Delimitation of the parts of the stapedial anlage
18 16 Chondrogenesis phase. Start of involution of the stapedial artery
20 18.5 Delimitation of the ossicular anlages. Cartilaginous phase. Disappearance of the stapedial artery
22 26 Delimitation of the interhyale
23 28 Anlage of the stapedial muscle tendon
Data from Table 1[43]   Links: middle ear


External Auditory Meatus Timeline
Period Week Description
Embryo week 8 Funnel-shaped tube continues medially into mesenchymal tissue, forms a curved path.
Fetus (first trimester) week 9 Ectodermal cells proliferate, fill the meatus lumen and form the "meatal plug".
Fetus (first trimester) week 10 Meatal plug bottom extends in a disc-like fashion, so that in the horizontal plane the meatus is boot-shaped with a narrow neck and the sole of the meatal plug spreading widely to form the future tympanic membrane medially. At the same time, the plug in the proximal portion of the neck starts to be resorbed.
Fetus (second trimester) week 13 Meatal plug disc-like, innermost surface in contact with the primordial malleus, contributes to formation of tympanic membrane.
Fetus (second trimester) week 15 Meatal plug innermost portion splits, leaving a thin ectodermal cell layer of immature tympanic membrane. The neck of the boot forms the border between the primary and secondary meatus, and is the last part to split.
Fetus (second trimester) week 16.5 The meatus is fully patent throughout entire length. Lumen is still narrow and curved. Epithelium cornification commences.
Fetus (second trimester) week 18 The meatus is now fully expanded to its complete form.
Links: outer ear | hearing | timeline     Reference[44]

Vision

Human Eye Development
Carnegie Stage Event
10 optic primordia appear.
11 Right and left optic primordia meet at the optic chiasma forming a U-shaped rim.
12 optic neural crest reaches its maximum extent and the optic vesicle becomes covered by a complete sheath,
13 By the end of the fourth week the optic vesicle lies close to the surface ectoderm. Optic evagination differentiation allows identification of optic part of retina, future pigmented layer of retina, and optic stalk. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode.
14 (about 32 days) Lens placode is indented by the lens pit, cup-shaped and still communicates with the surface by a narrowing pore.
15 (about 33 days) Lens pit is closed. The lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface.
16 (37 days) Growth of the lens body results in a D-shaped lens cavity. Perilental blood vessels (tunica vasculosa lentis) are visible. Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it.
17 - 19 Retinal pigment is visible and the retinal fissure is largely closed. Eyelids grooves deepen, eyelid folds develop, first below, and then above, the eye.
18 Mesenchyme invades the region between the lens epithelium and the surface ectoderm.
19 - 22 Eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19.
20 Lens cavity is lost and a lens suture begins to form. The inner canthus is established.
23 retina comprises the pigmented layer, external limiting membrane, proliferative zone, external neuroblastic layer, transient fiber layer, internal neuroblastic layer, nerve fiber layer, and internal limiting membrane. Eyelids closure is complete (Note - shown as still open in the Kyoto embryo).
Data from a study of human embryonic carnegie stages[7] and other sources.
Week: 1 2 3 4 5 6 7 8
Carnegie stage: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23


Human Eye Neural Crest Timeline
Carnegie Stage Event
9 an indication of mesencephalic neural crest
10 trigeminal, facial, and postotic components
11 crest-free zones are soon observable in rhombomere 1, 3, and 5
12 rhombomeres 6 and 7 neural crest migrate to pharyngeal arch 3 and then rostrad to the truncus arteriosus
13 nasal crest and the terminalis-vomeronasal complex are last of the cranial crest to appear
9 to 14 otic vesicle primordium descends
Week: 1 2 3 4 5 6 7 8
Carnegie stage: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Data from a study of 185 serially sectioned staged (Carnegie) human embryos.[1] Links: vision | neural crest | timeline |     Category:Timeline

Human Embryonic Eyelid Timeline
Carnegie Stage Event
10 optic primordia appear
13 By the end of the fourth week the optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode.
14 (about 32 days) the lens placode is indented by the lens pit.
15 (about 33 days) the lens pit is closed. The lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface.
16 (37 days) Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it.
17 - 19 grooves deepen, eyelid folds develop, first below, and then above, the eye.
19 - 22 eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19.
20 the inner canthus is established.
23 closure of the eyelids is complete (Note - shown as still open in some Kyoto embryo).
Data - from Kyoto embryos with Carnegie staging.[7]   Links: eyelid

Smell

Embryonic Smell Development
Week FA (GA) Carnegie Stage Event
week 4 (GA 6) 11 nasal epiblastic thickening appears
12 nasal field is well outlined
week 5 (GA 7) 15 continuous cellulovascular strand seen between the nasal groove and the olfactory field
week 6 (GA 8) 16 vomeronasal groove appears.
17 olfactory nerve is organized into two plexuses, lateral and medial, the latter mingled with the terminal-vomeronasal complex.
week 7 (GA 9) 18 olfactory bulb begins to appear
19 individualization of the olfactory bulb and nuclei, distinction between olfactory structures and terminal and vomeronasal ones begins to be clear.
week 8 (GA 10) 21 structure of the olfactory bulb is evident.
23 olfactory strands are well individualized, and olfactory and terminal-vomeronasal fibers are easily distinguishable.
Links: smell | sensory | timeline | Category:Timeline    Table Data Reference[45]

Cardiovascular

Heart

Human Heart Timeline
Characteristic Carnegie stage: 13 14 15 16 17 18 19 20 21 22 23
Septum primum
Foramen primum
Atrioventricular bundle
Atrioventricular cushions
Conotruncal ridges
Foramen secundum
Semilunar cusps
Conotruncal septum; atria
Closure primum foramen
Fusion atrioventricular cushions
Septum secundum and foramen ovale
Closure secondary interventricular foramen
Chordae tendineae
  Colour Coding: beginning to appear present    Table data[46]    Links: heart | Madrid Collection
Table 1. Comparison of Human and Murine Development  
Human Mouse
Carnegie
Stage
Post-ovulatory
Days
Size (mm)
Greatest Length
Theiler
Stage
Post-conception
Days
Size (mm)
Crown-rump
11 24 2.5 - 4.5 14 9 - 9.5 2.1
12 26 3 - 5 15 9.5 - 10.25 2.5
13 28 4 - 6 16 10.25 - 10.5 3.6
14 32 5 - 7 17 10.5 4.1
15 33 7 - 9 18 11 4.6
16 37 8 - 11 19 11.5 6 - 7
17 41 11 - 14 20 12 7
18 44 13 - 17 21 12.5 - 13 8.2
19 47.5 16 - 18 21 12.5 - 13 8.2
20 50.5 18 - 22 22 13.5 - 14 9.1
21 52 22 - 24 22 13.5 - 14 9.1
22 54 23 - 28 22 13.5 - 14 9.1
23 56.5 27 - 31 22 13.5 - 14 9.1
26 17.5 - 18 17.8

Notes: Human Embryonic Development | Carnegie Stages | Mouse Development | Theiler Stage | Post-conception Days | Carnegie Stage Comparison

Reference: Anderson RH. Teratogenecity in the setting of cardiac development and maldevelopment. (2016)

Cerebral Arterial

Cerebral Arterial Timeline
Carnegie Stage CRL (mm) Event
13 4 - 5 hindbrain (future posterior fossa) is supplied by two parallel neural arteries (or channels). These arteries obtain their blood supply from carotid-vertebrobasilar anastomoses given by the trigeminal artery (TA), the otic artery (OA), hypoglossal artery (HA), and the proatlantal artery (ProA)
14 5 - 8 basilar artery (BA) forms from the consolidation of the neural arteries.
15 7 - 12 vertebral arteries (VA) forms from transverse anastomoses between cervical intersegmental arteries, beginning with the ProA and proceeding downward to the 6th intersegmental artery,
16 11 - 12 (35 days) development of the middle cerebral artery (MCA) is first identified as small buds originating proximal to the anterior cerebral artery (ACA) on the anterior division of the primitive internal carotid artery (ICA).
19 16 - 18 middle cerebral artery (MCA) becomes more prominent, the plexi fuse into a single artery and further branches pierce the cerebral hemisphere.
20 18 stem of the ACA gives rise to the olfactory artery.
21 21-24 formation of the anterior communicating artery (ACOMM).
Early development - the posterior circulation relies almost entirely from blood supply coming from the anterior circulation through carotid-vertebrobasilar anastomoses.
Later development - as the posterior fossa structures and the occipital lobe grow, the posterior circulation becomes progressively independent from the anterior circulation with obliteration of the anterior-posterior anastomoses from caudal to rostral maintaining in the majority of adult only one connection between the distal basilar arteries with the carotid artery via the posterior communicating artery.
Data source[5])  Links: neural vascular

Placenta

Human Villi Timeline
Fertilization Age

(weeks)

Gestational Age

(weeks)

Vessel Lumen Diameter

(range in microns, µm)

Features
3 to 4 5 and 6 10 - 15
  • a complex network of cords and vessels with redundant connections
  • network comprises mainly cords, already connected together
  • vessels and cords are connected to each other without any interruptions
  • chorionic villus dominated by this network of vascular elements
  • vessels and cords are located centrally as well as peripherally and as a consequence contact the overlying trophoblastic layer
5 to 6 7 and 8 10 - 26
  • villi dominated by capillary network of vessels and cords
  • capillary network contains more vessels than cords
  • chorionic villus tip - regular small branched off (mesenchymal) chorionic villi are present containing CD31 positive cells
7 to 8 9 and 10 60 - 75 two central vessels

26 - 34 capillary network

  • villi have two large centrally located vessels
  • surrounded by and connected to a peripheral capillary network
  • capillary network contains vessels with a lumen in tight contact with overlying trophoblastic layer
  • villous projections also contain blind ending capillary sprouts
9 to 10 11 and 12 70 - 90 two central vessels

26 - 34 capillary network

  • immature intermediate villi characterized by two large vessels surrounded by a capillary network
  • capillary network has few cords
  • blind ending capillary sprouts off the capillary network
Vill development data based upon immunochemistry confocal laser scanning microscope (CLSM) study[47] with clinical gestational age (GA) from last menstrual period (LMP) and has been corrected for post-conception (fertilization) age, approximately 14 days later.

CD31 - (PECAM-1, Platelet Endothelial Cell Adhesion Molecule) is a cluster of differentiation molecule found on endothelial and other blood cells.

Liver

Human Embryonic Liver Development
Week
Carnegie Stage
Feature
Week 4

Carnegie stage 11
hepatic diverticulum development (ductal plate)
Carnegie stage 12
cell differentiation

septum transversum forming liver stroma

hepatic diverticulum forming hepatic trabeculae

Carnegie stage 13
epithelial cord proliferation enmeshing stromal capillaries
Week 5
Carnegie stage 14
hepatic gland and its vascular channels enlarge

hematopoietic function appeared

Week 7
Carnegie stage 18
obturation due to epithelial proliferation

bile ducts became reorganized (continuity between liver cells and gut)

Week 7 to 8
Carnegie stage 18 to Carnegie stage 23
biliary ductules developed in periportal connective tissue

produces ductal plates that receive biliary capillaries

Human data[3], see also liver development in the rat embryonic period (Carnegie stages 15-23).[48] (More? Detailed Timeline | Timeline human development)


Embryonic Liver Development Timeline  
Carnegie Stage Age (days) CRL (mm) Biliary system Vascular Hepatic parenchyma
14 33 7
  • Bile duct - primordial duct links primitive intestine and liver parenchyma. Thick-walled tube (95 µm diameter) small lumen (22 µm diameter).
  • Gall bladder - elongated tube further dilated, thick wall (125 µm diameter) and a narrow lumen (43 µm diameter).
  • Hepatic sinusoids - intra-hepatic vasculature present
  • Three venous tributaries flow into the liver sinusoids - right and left placental vein and a single vitelline vein.
  • Cords of liver cells fragmented by vascular network of hepatic sinusoids.
  • Between pericardial cavity (top) and mesonephros (bottom).
  • Upper pole of the liver lies close to the septum transversum and early ventricles.
  • Liver occupies the majority of abdominal cavity.
18 46 15
  • Bile duct (future common bile duct), and a common hepatic duct, in contact with liver parenchyma without penetration.
  • Primordium of accessory bile tract is an elongated and fusiform gall bladder projecting forward and by a short cystic duct that opens into common bile duct.
  • Bile duct empties into second part of duodenum on its posterior side.
  • Portal system visible - portal vein (100 µm diameter) arises from connection of upper mesenteric vein then at region of hepatic hilum (285 µm) divides into portal branches.
  • Left umbilical vein empties into anterior extremity of the left portal branch.
  • Ductus venosus (80 µm) connects the initial portion of left portal vein to the inferior vena cava.
  • Hepatic venous system 3 branches - left hepatic vein (120 µm in diameter), middle hepatic vein (220 􏰁µm in diameter) and right hepatic vein (160 µm in diameter). Flows into the sub-cardinal vein.
  • Liver parenchyma has two anatomical lobes (right and left lobe), separated by anteroposterior plane formed by placental vein.
21 53 22.5 Bile duct morphology as earlier stage. Common bile duct empties at the level of the proximal duodenum.
  • Portal vein arises from joining of splenic vein and superior mesenteric vein. At the level of the hepatic hilum, portal vein divides into two branches, right portal branch (420 µm in diameter) and left portal branch (540 µm in diameter). Right portal branch gives rise to a thin branch to caudate lobe. Ventral branch gives rise to segmental portal veins (VIII and V). Dorsal branch gives rise to the segmental portal veins (VI and VII).
  • Ductus venosus connects initial portion of left portal vein to inferior vena cava, just upstream from hepatic vein afferents.
  • Hepatic venous system as for previous stage.
Hepatic parenchyma a large rounded mass.
23 58 27 Bile duct morphology as earlier stage.
  • Portal venous system complete.
  • Ductus venosus (40 µm) connects initial portion of portal vein to middle hepatic vein.
  • hepatic venous system has changed very little from the previous stage. Three hepatic veins empty into inferior vena cava.
  • Liver parenchyma roughly oval shape, 2 symmetrical hepatic lobes. The quadrate and caudate lobes are identifiable.
  • Upper pole of the liver bounded above by diaphragm.
Data from a recent human study[49]

Links: liver | Carnegie stage 14 | 18 | 21 | 23 | simple embryonic timeline | Timeline human development

Pancreas

Human Pancreas Timeline
Carnegie Stage Days Event
10 25-27 distal endoderm foregut
12 29-31 pancreatic duodenal endoderm

extra-hepatic billiard duct

13 30-33 pancreatic bud
19 47 "trunk" progenitor

"tip" progenitor

23 8 weeks + fetal beta cell

ductal cell

fetal 14 weeks acinar cell
  Table data[50]   Links: pancreas | exocrine pancreas | pancreas molecular timeline | timeline
Human Pancreas Timeline  
Human Pancreas Timeline
Carnegie Stage Days Event
10 25-27 distal endoderm foregut
12 29-31 pancreatic duodenal endoderm

extra-hepatic billiard duct

13 30-33 pancreatic bud
19 47 "trunk" progenitor

"tip" progenitor

23 8 weeks + fetal beta cell

ductal cell

fetal 14 weeks acinar cell
  Table data[50]   Links: pancreas | exocrine pancreas | pancreas molecular timeline | timeline
Human Pancreas Timeline
Carnegie Stage Days Molecular Event
10 25-27 FOXA2, SOX17 (dorsal), SHH (ventral) distal endoderm foregut
12 29-31 PDX1, FOXA2, SOX17, GATA4, SOX9 (weak)

SOX9, FOXA2, PDX1 (weak)

pancreatic duodenal endoderm

extra-hepatic billiard duct

13 30-33 PDX1, FOXA2, GATA4, NKX6.1, SOX9 pancreatic bud
19 47 PDX1, FOXA2, GATA4, NKX6.1, SOX9

PDX1, FOXA2, GATA4, NKX6.1, SOX9

"trunk" progenitor

"tip" progenitor

23 8 weeks + PDX1, FOXA2, GATA4, NKX6.1, NKX2.2, ISL1

SOX9, FOXA2, PDX1 (weak)

fetal beta cell

ductal cell

fetal 14 weeks GATA4 acini cell
  Table data[50]   Links: pancreas | exocrine pancreas | timeline
Human Pancreas Molecular Timeline  
Human Pancreas Timeline
Carnegie Stage Days Molecular Event
10 25-27 FOXA2, SOX17 (dorsal), SHH (ventral) distal endoderm foregut
12 29-31 PDX1, FOXA2, SOX17, GATA4, SOX9 (weak)

SOX9, FOXA2, PDX1 (weak)

pancreatic duodenal endoderm

extra-hepatic billiard duct

13 30-33 PDX1, FOXA2, GATA4, NKX6.1, SOX9 pancreatic bud
19 47 PDX1, FOXA2, GATA4, NKX6.1, SOX9

PDX1, FOXA2, GATA4, NKX6.1, SOX9

"trunk" progenitor

"tip" progenitor

23 8 weeks + PDX1, FOXA2, GATA4, NKX6.1, NKX2.2, ISL1

SOX9, FOXA2, PDX1 (weak)

fetal beta cell

ductal cell

fetal 14 weeks GATA4 acini cell
  Table data[50]   Links: pancreas | exocrine pancreas | timeline

Spleen

Human Spleen Development
Embryonic Week
Carnegie Stage
Feature
Week 5
14
Carnegie stage 14 to 17

appears as a bulge in the dorsal mesogastrium. Mesothelium pseudostratified.

15
Week 6
16
Mesothelium (pseudostratified} replaced with high columnar cells and then low columnar cells.
17
Basement membrane present after this stage.
Week 7
18
Hematopoietic cells detected.
Week 8
20
Spleen is now apparent. Mesenchymal cells differentiated from cells in dorsal mesogastrium. Sinus and hilus formation after this stage.
23
Arteries and veins parallel entries at this stage.
Fetal Week FA
Gestational Age GA
Feature
Week 15
Week 17
reticulum cells (alpha-smooth muscle actin-positive) scattered around the arterioles
Week 18-21
Week 20-23
reticulum cells increase in number and began to form a reticular framework.
Accumulation of T and B lymphocytes within this framework, and a primitive white pulp was observed around the arterioles.
Week 22
Week 24
reticular framework antigenic diversity, and T and B lymphocytes were segregated in the framework.
T lymphocytes were sorted into the alpha-SMA-positive reticular framework, and the periarteriolar lymphoid sheath (PALS) was formed around the arteriole.
B lymphocytes aggregated in eccentric portions to the PALS and formed the lymph follicle (LF, reticular framework alpha-SMA-negative).
Week 24
Week 26
marginal zone appears in reticular framework around the white pulp.
Human embryonic data[51] and fetal data [33]   Links: spleen | Kyoto Collection | human timeline

Respiratory

Respiratory Stages - Species Comparison - Stages Gestational age (days)
Species Term Embryonic Pseudoglandular Canalicular Saccular
human 280 < 42 52 - 112 112 - 168 168
primate 168 < 42 57 - 80 80 - 140 140
sheep 150 < 40 40 - 80 80 - 120 120
rabbit 32 < 18 21 - 24 24 - 27 27
rat 22 < 13 16 - 19 19 - 20 21
mouse 20 < 9 16 18 19
Data modified from[52]   

Links: respiratory | Respiratory Comparison | Mouse Human Respiratory | Mouse respiratory stages | mouse | rat | rabbit | Timeline Comparisons

Age (months) Alveoli (million) Respiratory Airways (million) Generations of Airways
Birth 24 1.5
3 86 1.8
3 77 2.5 21
3 73 2.0
7 112 3.7
13 129 4.5 22
16 127 4.7
22 160 7.1
48 257 7.9
98 280 14.0 23
Adult 296 14.0 23
Data modified from [53]

  Links: respiratory | Respiratory Comparison | Mouse Human Respiratory | Mouse respiratory stages | mouse | rat | rabbit | Timeline Comparisons

Genital

Seminal Vesicle Timeline
Week Fetal CRL mm Event
13 80 seminal vesicles appear as lateral evaginations or out-pocketings from the lower portion of the mesonephric ducts (Wolffian ducts). At this stage their lateral diameter is always greater than the anteroposterior length.
14 100 sacculations or diverticula of the vesicles as evaginations of the walls of the vesicles. At this time 3 small but distinct sacculations may be counted at a given level in each vesicle.
19 170 dilatation of the mesonephric ducts in their lower portion, to form the ampullae of the deferent ducts. Sacculations of the ampullae in the form of slight but definite irregularities of their lumina. Each vesicle at this stage shows from 3 to 8 distinct sacculations at a given level. The lateral and antero—posterior diameters are now about equal.
21 180 sacculations of the mesonephric ducts have become well developed and the dilatation of the ducts to form the ampullae have assumed very nearly their proportions at birth.
25 220 vesicles and ampullae have assumed practically their adult form as regards their general topography and arrangement of sacculations. At a single level may be counted from~nine to twelve separate diverticula.
25 to 31 220 to 275 prostatic utricle opens into the posterior urethra. At the latter date has a bifid lumen showing the union of two partially fused tubes. At this stage 5 to 7 distinct sacculations in each vesicle at a given level.
Birth vesicles show at a given level 7 distinct sacculations at one time. At this stage many of the diverticula are traversed by a network of fine trabeculae.
Data[54]   Links: seminal vesicle | timeline

Ovary

Human Ovary Timeline
Time Carnegie Stage Event
24 days 11 intermediate mesoderm, pronephros primordium
28 days 12 mesonephros and mesonephric duct
35 days 14 uteric bud, metanephros, urogenital ridge
42 days 17 cloacal divison, gonadal primordium (indifferent)
49 days 19 paramesonephric duct, gonadal differentiation
6-7 weeks (GA 8-9 weeks) primordial germ cell mitosis proliferation commences
56 days 23 paramesonephric duct fusion (female)
12-14 weeks (GA 14-16 weeks) fetal primordial germ cell meiosis germ cell differentiation, formation of syncitial clusters of oogonia
15-18 weeks (GA 17–20 weeks) fetal breakdown of syncitial clusters and assembly of primordial follicles
Links: ovary | oocyte | timeline | Category:Timeline


Human Ovary Follicle Number Timeline

Human ovary non-growing follicle model.jpg

Bone

Shoulder Development Timeline
Carnegie Stage Event
17 chondrogenic progenitor of the humerus and the medial border of the scapula can be observed.
18 chondrogenic progenitor for rest of the scapula appears.
19 glenohumeral joint will begin delaminating and showing a looser central band (interzone). Denser lateral bands will join the humeral head (caput humeri) and the margins of the articular surface of the scapula, thus forming the glenoid labrum (glenoid ligament).
21 long head of the biceps tendon present
22 glenoid labrum (glenoid ligament) present
23 coracohumeral ligament present
Week
Fetal Week 10 osteogenic process begins in the humeral head. Primitive glenohumeral ligament present
Fetal Week 11 osteogenic process begins in the scapula
Links: shoulder | joint | limb | timeline     Data from human histological study.[55]
Human Pelvis Development
Carnegie Stage Event
18 chondrification centres of the ilium, ischium, and pubis first appears. Located around the acetabulum and grew radially.
20 iliac crest formed while the iliac body's central part remained chondrified.
22 Sacroiliac joint forms.
22 Iliac body is discoid. The growth rate was greater in the ilium than in the sacrum-coccyx, pubis, and ischium.
23 Articulation of the pubic symphysis, connection of the articular column in the sacrum, and Y-shape connection of the three parts of the hip bones to the acetabulum.
Early Fetal connection of the ischium and pubic ramus.
Data from human CT and MRI study.[56]
   Links: pelvis | pelvis timeline | joint | limb | timeline
Table Of Ossification Of The Bones Of The Superior Extremity
Bone Centres Time of appearance of centre Union of primary and secondary centres; remarks.
Clavicle Diaphysis 6th week There are two centres in the shaft, a medial and a lateral. These blend on the 45th day (Mall). Shaft and epiphysis unite between the 20th and 25th years.
Sternal epiphysis 18th to 20th year
Scapula Primary centres: The chief centre appears near the lateral angle. The subcoracoid centre appears at the base of the coracoid process and also gives rise to a part of the superior margin of the glenoid fossa. The coracoid process joins the body about the age of puberty. The acromial epiphysis centres (two or three in number) fuse with one another soon after their appearance and with the spine between the 22nd and 25th years (Quain); 20th year (Wilms). The subcoracoid and the epiphysis of the coracoid process, the glenoid fossa, the inferior angle, and the vertebral margin join between the 18th and 24th years in the order mentioned (Sappey).
1. That of the body, the spine, and the base of the glenoid cavity. 8th week (Mall) 1
2. Goraooid process 1st year
3. Subcoracoid 10th to 12th year
Epiphyses:
Acromial epiphyses 15th to 18th year
Epiphysis of the inferior angle. 16 to 18th year
Epiphyses of the vertebral border. 18th to 20th year
Epiphyses of upper surface of coracoid. 16th to 18th year.
Epiphysis of surface of glenoid fossa. 16th to 18th year.
Humerus Diaphysis 6th to 7th week (Mall) The epiphyses of the head, the tuberculum majus and the tuberculum minus (the last is inconstant) unite with one another in 4th-6th year and with the shaft in 20th-25th year. The epiphyses of the capitulum, lateral epicondyle, and trochlea unite with one another and then in the 16th-17th year join the shaft. The epiphysis of the medial epicondyle joins the shaft in the 18th year.
Epiphyses:
Head 1st to 2d year
Tuberculum majus 2d to 3d year
Tuberculum minus 3d to 5th year
Capitulum 2d to 3d year
Epioondylus med 5th to 8th year
Lateral margin of trochlea 11th to 12th year
Epicondylus lat 12th to 14th year
Radius Diaphysis 7th week (Mall) The superior epiphysis and shaft unite between the 17th and 20th years. The inferior epiphysis and shaft about the 21st year (Pryor); M 21st year, F 21st-25th year (Sappey). Sometimes an epiphysis is found m the tuberosity (R. and K.) and in the styloid process (Sappey).
Epiphyses:
Carpal end F 8th month - M 15th month (Pryor)
Humeral end 6th-7th year
Ulna Diaphysis 7th week The centre for the shaft of the ulna arises a few days later than that for the radius. The proximal epiphysis is united to the shaft about the 17th year; the inferior epiphysis between the 18th and 20th years; F 20th - 21st years, M 21st - 24th years (Sappey). There is sometimes an epiphysis in the styloid process (Sohwegel) and in the tip of the olecranon process (Sappey).
Epiphyses:
Carpal end F 6th-7th year - M 7th-8th year (Pryor)
Humeral end 10th year
Carpus Os capitatum F 3d-6th month M 4th-10th month The navicular sometimes has two centres of ossification (Serres. Rambaud and Renault). Serres and Pryor have described two centres of ossification in the lunatum. Debierre has described two centres in the pisiform, one in a girl of eleven, the other in a boy of twelve. The OS hamatum may have a special centre for the hamular process. Pryor has found two centres in the triquetrum. Pryor (1908), describes the centres of ossification of the carpal bones as assuming shapes characteristic of each bone at an early period.
Os hamatum F 5th-10th month M 6th-12th month
Os triquetrum F 2d-3d year M about 3 years
Os lunatum F 3rd-4th year M about 4 years
Os naviculare F at 4 years, or early in 5th year M about 5 years
Os mult. maj. F 4th-5th year M 5th-6th year
Osmult. min. F 4th-5th year M 6th-6th year
Os pisiforme F 9th-10th year M 12th-3th year
Metacarpals Diaphyses 9th week (Mall) The centres for the shafts of the second and third metacarpals are the first to appear. There may be a distal epiphysis for the first metacarpal and a proximal epiphysis for the second. Pryor (1906). found the distal epiphysis of the first metacarpal in about 6 per cent, of cases. It is a family characteristic. It arises before the 4th year and unites later. Pryor found the proximal epiphysis of the second metacarpal in six out of two hundred families. It unites with the shaft between the 4th and 6th-7th year; sometimes, however, not until the 14th year. In the seal and some other animals all the metacarpals have proximal and distal epiphyses (Quain). The epiphyses join the shafts between the 15th and 20th years. There may bean independent epiphysis for the styloid process of the 5th metacarpal. The epiphysis of the metacarpal of the index finger appears first. This is followed by those of the 3d, 4th, 5th, and 1st digits.
Proximal epiphysis of the first metacarpal 3d year
Distal epiphyses of the metacarpals 2d year
Phalanges Diaphyses 9th week (Mall)
First row Proximal epiphyses 1st-3rd year (Pryor) The shafts of the phalanges of the second and third fingers are the first to show centres of ossification. The phalanges of the little finger are the last, the epiphysis in the middle finger is the first to appear. This is followed by those of the 4th, 2d, 5th, and 1st digits.
Middle row Diaphyses 11th-12th week (Mall) The centres in the shafts of this row are the last to appear. The epiphysis of the phalanx of the middle finger is the first to appear. This is followed by those of the ring, index, and little finger (Pryor).
Proximal epiphyses 2nd-3rd year
Terminal row Diaphyses 7th-8th week The terminal phalanx of the thumb is the first to show a centre of ossification in the shaft. This is the first centre of ossification in the hand. It is developed in connective tissue while the centres of the other phalanges are developed in cartilage (Mall). The epiphysis of the ungual phalanx of the thumb is followed by those of the middle, ring, index, and little fingers. The fusion of the epiphyses of the phalanges with the diaphyses takes place in the 18th-20th year.
Proximal epiphyses 2nd-3rd year
Sesamoid bones Ossification begins generally in the 13th - 14th years, and may not take place until after middle life (Thilenius). For table of relative frequency in the embryo and adult see p. 385.
Days and weeks refer to the prenatal, years to the postnatal period. M = male F = female.

According to Poirier, Traite d'Anatomie, p. 138, two centres appear in the eighth week, and unite in the third month to form a centre of ossification for the body of the scapula.

Links: limb | bone | upper limb ossification timeline | lower limb ossification timeline | Historic - Chapter 11 Development of the Skeleton | timeline | Category:Timeline     Table Data Reference[57]
Table Of Ossification Of The Bones Of The Inferior Extremity
Bone Centres Time of appearance of centre Time of fusion: general remarks
Os coxae Os ilium 56th day (Mall) The rami of the ischium and the pubis are united by bone in the 7th or 8th year (Quain) ( 12-14 year Sappey). In the acetabulum the three hip bones are separated by a Y-shaped cartilage until after puberty. In this cartilage between the ilium and pubis the "os acetabuli" appears between the ninth and twelfth years. This bone, variable in size, forms a greater or less part of the pubic portion of the articular cavity. Leche (1884). Krause (1885), and many others consider it primarily an independent bone. About puberty between the ilium and ischium and over the acetabular surfaces of these bones small irregular epiphyseal centres appear. The os acetabuli becomes imited to the pubic bone about puberty and soon afterwards the acetabular portions of the ilium and ischium and the ischium and pubis begin to become united by bone. The acetabular portions of the pubis and ilium are unite a little later. Osseous union takes place earlier on the pelvic than on the articular surface of the acetabulum. The union of the several primary centres and the epiphyses is usually completed about the twentieth year.
Os ischii 105th day (Mall)
Os pubis 4th to 5th fetal month
Os acetabuli. 9th to 12th year
Epiphyses:

Those of the acetabulum

Soon after puberty
Crest of ilium Soon after puberty Fuses with main bone 20th to 25th year
Tuberosity of ischium Soon after puberty Fusion begins in the 17th year and is completed between the 20th and 24th years (Sappey)
Ischial spine Soon after puberty 18th to 20th year (Poirier).
Ant. inf. spine of ilium Soon after puberty 18th to 20th year (Poirier)
Symphysis end of os pubis (1 or 2 centres) 18th to 20th year (Sappey) After the 20th year
Femur Diaphysis 43d day (Mall)
Epiphyses:

Distal end

Shortly before birth1 20th to 24th year
Head 1st year 18th to 19th year
Great trochanter 3d to 4th year (Osseous granules soon after birth, (Poirier) 18th year
Small trochanter 13th to 14th year

8th year (Sappey)

17th year (Quain)

Proximal epiphysis 18th to 22d year (Poirier)

Patella 3d to 5th year The osseous patella reaches its definitive form soon before puberty
Tibia Diaphysis 44th day (Mall)
Epiphyses:

Proximal end

About birth 19th to 24th year (Sappey)
Distal end 2d year 16th to 19th year
Tubercle (occas.) 13th year Fuses with epiphysis of the proximal end and then with this to the diaphysis
Fibula Diaphysis 55th day (Mall).
Epiphyses:

Distal end

2d year 20th to 22d year
Proximal end 3d to 5th year 22d to 24th year
Calcaneus Chief centre 6th fetal month The chief nucleus is endochondral. A periosteal nucleus appears frequently in the 4-5 fetal month (Hasselwander)
Epiphysis (distal end) 10th year (Quain)

7th-8th year ( Sappey)

15th-16th year (Quain)

16th-18th year (Poirier)

M 17-21, average 20 years

F 13-17, average 16 years (Hasselwander)

Talus 6th fetal month (Hasselwander) In the 7th-8th year the posterior part of the talus, the os trigonum, is frequently ossified from a special centre (v. Bardeleben). It fuses about the 18th year.
Cuboid About birth
Cuneiform III 1st year
Cuneiform I 2d-3d year
Cuneiform II 3d-4th year
Navicular 4th-5th year
Metatarsals Diaphyses 8th-10th week According to v. Bardeleben a second centre of ossincation appears much later than the primary in the navicular, and finally about the time of puberty a medial epiphyseal centre arises.
Epiphyses 3d-8th year The centre for the 2d metatarsal usually appears first, then come the 3rd, 4th, 1st and 5th. The epiphysis of the 1st metatarsal appears at the proximal end of the bone: the other epiphyses arise at the distal ends of the metatarsals. There may be a distal epiphysis in the first metatarsal also.2 In some instances a proximal epiphysis is formed on the tuberosity of the fifth metatarsal (Gruber). The epiphyses unite with the shafts in the 17-21 year in males and in the 14-19 year in females. (Hasselwander).
Phalanges:
Terminal row Diaphyses 58th day (Mall)
Epiphyses (distal) 4th year M 13-23, average 16-21 year.

F 13-17, average 14-17 year (Hasselwander).

Middle row Diaphyses 4th-10th fetal month
Epiphyses 3d year M 15-19 year

F 13-16 year (Hasselwander)

Proximal row Diaphyses 3d fetal month
Epiphyses 3d year M 15-17 year.

F 14-15 year (Hasselwander)

The centres for the shafts of the phalanges often appear double, one for the dorsal and one for the plantar surface. The centres for the medial phalanges in each row usually appear before the more laterally placed centres. The centre for the 5th terminal phalanx appears much later than the other centres in this row (Mall). According to Rambaud and Renault the epiphyses arise each from two centres which fuse together. In the terminal phalanx of the great toe the ossification centre of the epiphysis often appears as early as the second or even the first year. (Hasselwander)

Sesamoid bones of the great toe M 14th year

F 12th-13th year

Ossification may begin in the 8th year in females, in the 11th in males (Hasselwander).
  1. Poirier, Traite d'Anatomie, vol. 1. page 227, gives a summary of the literature on the time of the appearance of this epiphysis. The epiphysis has some medico-legal importance, since its presence or absence has been utilized to determine whether a child is born at term. Schwegel found it to appear between birth and the third year; Casper in the ninth fetal month. Hartmann found it lacking in 12 percent, of cases at birth and in 7 per cent, of cases present as early as the eighth fetal month.
  2. Mayet has described two centres of ossification for the proximal epiphysis of the first metatarsal, one of which represents the real metatarsal of the first digit.
Days and weeks refer to the prenatal, years to the postnatal period. M = male F = female.

According to Poirier, Traite d'Anatomie, p. 138, two centres appear in the eighth week, and unite in the third month to form a centre of ossification for the body of the scapula.

Links: limb | bone | upper limb ossification timeline | lower limb ossification timeline | Historic - Chapter 11 Development of the Skeleton | timeline | Category:Timeline     Table Data Reference[57]
Bone - Appearance and Fusion of Epiphyses Timeline
Before birth:
Both sexes    Appearance     Head of humerus, distal femur, proximal tibia, calcaneum, talus
Female   Appearance   Cuboid
During first year:
Both sexes   Appearance   Hamate, capitate, head of femur, third cuneiform
Female   Appearance   Capitulum, distal radius, distal tibia, distal fibula
Male   Appearance   Cuboid
During second year:
Both sexes   Appearance   Proximal phalanges of inner four fingers
Female   Appearance   First metacarpal, distal phalanges of thumb, middle and ring fingers,

tarsal navicular, first and second cuneiforms

Male   Appearance   Capitulum, distal epiphysis of radius, distal fibula
At age of 2:
Both sexes   Appearance   Innerfourmetacarpals,firstmetatarsal,proximalphalangesoftoes, distal phalanx of hallux
Female   Appearance   Proximal phalanx of thumb, middle row of phalanges of fingers
Male   Appearance   First metacarpal, distal phalanx of thumb, and distal phalanx of

index,firstcuneiform

At age of 3:
Female   Appearance   Patella, proximal fibula, second metatarsal, third metatarsal, middle phalangesof second, third and fourth toes, distal phalanges of third and fourth toes
Male   Appearance   Triquetrum, proximal phalanx of thumb, middle phalanges of middle and ring fingers, tarsal navicular, second cuneiform
At age of 4:
Both sexes   Appearance   Fourth metatarsal
Female   Appearance

Fusion

Head of radius, fifth metatarsal

Greater tubercle to head of humerus

Male   Appearance   Lunate, middle phalanges of index and litle fingers, distal phalanges

of middle and ring fingers, second metatarsal, third metatarsal, middle phalanx of second toe

At age of 5:
Both sexes   Appearance   Navicular (carpal), multangulum majus, greater trochanter, distal

phalanx of second toe

Female   Appearance   Medial epicondyle, distal ulna, lunate, triquetrum, multangulum

minus, distal phalanx of index

Male   Appearance
Head of radius, distal phalanx of litle finger, patella, proximal

fibula, fifth metatarsal, middle phalanges of third and fourth toes, distal phalanges of third and fourth toes

Fusion Greater tubercle to head of humerus
At age of 6:
Male   Appearance   Medial epicondyle, distal ulna, multangulum minus
At age of 7:
Female   Appearance   Distal phalanx of litle finger
Fusion Rami ofischium and pubis
At age of 8:
Both sexes   Appearance   Apophysis of calcaneus
Female   Appearance   Olecranon
At age of 9:
Female   Appearance   Trochlea, pisiform
Male   Fusion   Rami of ischium and pubis
At age of 10:
Male   Appearance   Trochlea, olecranon
At age of 11:
Female   Appearance   Lateral epicondyle
Male   Appearance   Pisiform
At age of 12:
Male   Appearance   Lateral epicondyle
At age of 13:
Female   Appearance   Proximal sesamoid of thumb
Fusion   Lower conjoint epiphysis of humerus, distal phalanx of thumb, bodies ilium, ischium and pubis
Male   Fusion   Capitulum to trochlea and lateral epicondyle
At age of 14:
Female   Appearance   Acromion, iliac crest, lesser trochanter
Fusion   Olecranon, upper radius, proximal phalanx of ring finger, distal phalanx of thumb, head of femur, greater trochanter, distal tibia and fibula, apophysis calcaneus, first metatarsal, proximal phalanges oftoes
Male   Appearance   Proximal sesamoid of thumb, base of fifth metatarsal
At age of 15:
Both sexes   Appearance   Sesamoid of little finger
Fusion   Distal phalanges of second, third and fourth toes
Female   Appearance   Sesamoid of index and little fingers
Fusion   Medial epicondyle, first metacarpal, proximal phalanx of thumb, distal phalanges of inner four fingers, proximal tibia, outer four metatarsals, middle phalanx of second toe, distal phalanges of innerfourtoes
Male   Appearance   Acromion
Fusion   Ilium, ischium and pubis
At age of 16:
Female   Appearance   Distal sesamoid of thumb, tuber ischii
Fusion   Inner four metacarpals, proximal phalanges of index, middle and litle fingers, middle phalanges of fingers
Male   Fusion   Lower conjoint epiphysis of humerus, medial epicondyle, olecranon, head of radius, distal phalanx of middle finger, apophysis of calcaneus
At age of 17:
Both sexes   Fusion   Acromion
Female   Fusion   Upper conjoint epiphysis of humerus, distal ulna, distal femur, proximal fibula
Male   Appearance   Distalsesamoidofthumb
Fusion   First metacarpal, proximal phalanges of thumb and ring finger, middle phalanges, index, middle and ring fingers, distal phalanges of thumb, index, ring and little fingers, head of femur, greater trochanter,distal tibia and fibula, metatarsals, proximal phalanges of toes, middle phalanx of second toe, distal phalanx of hallux
At age of 18:
Female   Fusion   Distal radius
Male   Fusion   Inner four metacarpals, proximal phalanges of index, middle and litle fingers, middle phalanges of litle finger, proximal tibia
At age of 19:
Male   Appearance   Sesamoid of index, tuber ischii
Fusion   upper conjoint epiphysis of humerus, distal radius and ulna, distal femur, proximal fibula
At age of 20:
Both sexes   Fusion   Iliac crest
Male   Fusion   Tuber ischii
At age of 21:
Both sexes   Appearance   Clavicle
Female   Fusion   Tuber ischii
At age of 22:
Both sexes   Fusion   Clavicle
Table Data: Flecker (1932)[58] | Original table | bone timeline
Bone - Appearance and Fusion of Epiphyses Timeline  
Bone - Appearance and Fusion of Epiphyses Timeline
Before birth:
Both sexes    Appearance     Head of humerus, distal femur, proximal tibia, calcaneum, talus
Female   Appearance   Cuboid
During first year:
Both sexes   Appearance   Hamate, capitate, head of femur, third cuneiform
Female   Appearance   Capitulum, distal radius, distal tibia, distal fibula
Male   Appearance   Cuboid
During second year:
Both sexes   Appearance   Proximal phalanges of inner four fingers
Female   Appearance   First metacarpal, distal phalanges of thumb, middle and ring fingers,

tarsal navicular, first and second cuneiforms

Male   Appearance   Capitulum, distal epiphysis of radius, distal fibula
At age of 2:
Both sexes   Appearance   Innerfourmetacarpals,firstmetatarsal,proximalphalangesoftoes, distal phalanx of hallux
Female   Appearance   Proximal phalanx of thumb, middle row of phalanges of fingers
Male   Appearance   First metacarpal, distal phalanx of thumb, and distal phalanx of

index,firstcuneiform

At age of 3:
Female   Appearance   Patella, proximal fibula, second metatarsal, third metatarsal, middle phalangesof second, third and fourth toes, distal phalanges of third and fourth toes
Male   Appearance   Triquetrum, proximal phalanx of thumb, middle phalanges of middle and ring fingers, tarsal navicular, second cuneiform
At age of 4:
Both sexes   Appearance   Fourth metatarsal
Female   Appearance

Fusion

Head of radius, fifth metatarsal

Greater tubercle to head of humerus

Male   Appearance   Lunate, middle phalanges of index and litle fingers, distal phalanges

of middle and ring fingers, second metatarsal, third metatarsal, middle phalanx of second toe

At age of 5:
Both sexes   Appearance   Navicular (carpal), multangulum majus, greater trochanter, distal

phalanx of second toe

Female   Appearance   Medial epicondyle, distal ulna, lunate, triquetrum, multangulum

minus, distal phalanx of index

Male   Appearance
Head of radius, distal phalanx of litle finger, patella, proximal

fibula, fifth metatarsal, middle phalanges of third and fourth toes, distal phalanges of third and fourth toes

Fusion Greater tubercle to head of humerus
At age of 6:
Male   Appearance   Medial epicondyle, distal ulna, multangulum minus
At age of 7:
Female   Appearance   Distal phalanx of litle finger
Fusion Rami ofischium and pubis
At age of 8:
Both sexes   Appearance   Apophysis of calcaneus
Female   Appearance   Olecranon
At age of 9:
Female   Appearance   Trochlea, pisiform
Male   Fusion   Rami of ischium and pubis
At age of 10:
Male   Appearance   Trochlea, olecranon
At age of 11:
Female   Appearance   Lateral epicondyle
Male   Appearance   Pisiform
At age of 12:
Male   Appearance   Lateral epicondyle
At age of 13:
Female   Appearance   Proximal sesamoid of thumb
Fusion   Lower conjoint epiphysis of humerus, distal phalanx of thumb, bodies ilium, ischium and pubis
Male   Fusion   Capitulum to trochlea and lateral epicondyle
At age of 14:
Female   Appearance   Acromion, iliac crest, lesser trochanter
Fusion   Olecranon, upper radius, proximal phalanx of ring finger, distal phalanx of thumb, head of femur, greater trochanter, distal tibia and fibula, apophysis calcaneus, first metatarsal, proximal phalanges oftoes
Male   Appearance   Proximal sesamoid of thumb, base of fifth metatarsal
At age of 15:
Both sexes   Appearance   Sesamoid of little finger
Fusion   Distal phalanges of second, third and fourth toes
Female   Appearance   Sesamoid of index and little fingers
Fusion   Medial epicondyle, first metacarpal, proximal phalanx of thumb, distal phalanges of inner four fingers, proximal tibia, outer four metatarsals, middle phalanx of second toe, distal phalanges of innerfourtoes
Male   Appearance   Acromion
Fusion   Ilium, ischium and pubis
At age of 16:
Female   Appearance   Distal sesamoid of thumb, tuber ischii
Fusion   Inner four metacarpals, proximal phalanges of index, middle and litle fingers, middle phalanges of fingers
Male   Fusion   Lower conjoint epiphysis of humerus, medial epicondyle, olecranon, head of radius, distal phalanx of middle finger, apophysis of calcaneus
At age of 17:
Both sexes   Fusion   Acromion
Female   Fusion   Upper conjoint epiphysis of humerus, distal ulna, distal femur, proximal fibula
Male   Appearance   Distalsesamoidofthumb
Fusion   First metacarpal, proximal phalanges of thumb and ring finger, middle phalanges, index, middle and ring fingers, distal phalanges of thumb, index, ring and little fingers, head of femur, greater trochanter,distal tibia and fibula, metatarsals, proximal phalanges of toes, middle phalanx of second toe, distal phalanx of hallux
At age of 18:
Female   Fusion   Distal radius
Male   Fusion   Inner four metacarpals, proximal phalanges of index, middle and litle fingers, middle phalanges of litle finger, proximal tibia
At age of 19:
Male   Appearance   Sesamoid of index, tuber ischii
Fusion   upper conjoint epiphysis of humerus, distal radius and ulna, distal femur, proximal fibula
At age of 20:
Both sexes   Fusion   Iliac crest
Male   Fusion   Tuber ischii
At age of 21:
Both sexes   Appearance   Clavicle
Female   Fusion   Tuber ischii
At age of 22:
Both sexes   Fusion   Clavicle
Table Data: Flecker (1932)[58] | Original table | bone timeline

Muscle

Abdominal Wall Muscle Timeline
Carnegie Stage Day Mouse Event
14 33 E10.5 mesoderm of primary body wall non-compact, coalesced in the ventral midline to create the abdominal cavity. Liver and stomach present. Dermomyotomes that are derived from somites have been formed.
16 40 Migration distance about 25% of the hemicircumference of the abdominal cavity. Lateral plate mesoderm has become more condensed and thicker in the area around the myoblasts. Primary abdominal wall ventral to this region was thinner and less dense. Suggests both myoblasts and connective tissue may migrate into the primary body wall or active cell proliferation.
17 42 E11.5 cells now migrated about 50% of the distance to the ventral midline. Inner and outer layers not yet not discernible.
18 44 E12.5 Separation of myoblasts into distinct inner and outer layers. Myoblasts in both inner and outer layers began to exhibit unidirectional orientation. Abdominal wall thicker (500 μm) in region where secondary structures forming compared with primary body wall region (260 μm). More dorsally positioned regions, outermost layer of connective tissue comprised approximately half of this thickness.
19 48 Segregation of the myoblasts into four distinct muscle groups with unidirectional orientation of myoblasts. Myoblasts migrated over half of the distance to the ventral midline. Abdominal wall remains thickest in the area where the muscles migrated and again the outermost layer of connective tissue comprises approximately half of the total thickness of the abdominal wall in this region. Primary abdominal wall that is ventral to the migrating myoblasts noticeably thinner. Human rectus completely separated after migrating over half the distance to the midline. In mouse, the rectus is not segregated from the other muscles until reaching the midline.
21 54 E14.5 Myoblasts have reached the ventral midline and myotubes were present and oriented uniformly within all muscle groups. Rectus abdominis formed distinct bundles of muscle indicating that development and differentiation of this muscle were more prominent in humans than in mice. Connective tissue layers form majority of the thickness of the abdominal wall, outermost layer of connective tissue majority of thickness.
23 58 E15.5 Rectus muscle forms 2 or 3 distinct layers and myotube orientation remained uniform in all muscles. External oblique and internal oblique expand in terms of thickness. Transversus remained a thin layer of muscle. Thickness of the connective tissue was reduced. The orientation of connective tissue layers in the obliques and transversus abdominis was dorsal to ventral.
Table Data[9]


For additional muscle timelines see the page - Muscle Development Timeline

Adipose

Adipose Tissue Timeline
Anatomical Region Specific Location Start
(weeks)
CRL (mm) Complete
(weeks)
CRL (mm)
Head Buccal pad 14 100 17 153
Cheek 14.5 103 17 150
Chin 14.5 103 17 150
Ocular pad 15 113 19.5 170
Neck Neck 15 113 19.5 170
Thorax Anterior wall 16 135 19.5 170
Posterior wall 15 113 20.5 190
Mammary 14.5 106 17.5 156
Abdomen Abdominal wall 14.5 106 20.5 190
Perirenal 15 113 20.5 190
Upper limb Shoulder 15 113 23.5 216
Forearm 16 131 20.5 190
Arm 16 131 20.5 190
Hand 16 131 l9.5 172
Lower limb Gluteal 16 131 20.5 190
Thigh 16.5 141 22.5 212
Leg 16 131 22.5 212
Foot 16 131 19.5 170
Table Notes - weeks are fertilization age (FA), not GA, both male and female data are combined.

Table Data source[59]   Links: adipose | Second Trimester

Nerve Endings

Comparison Human and Chick Neural Endings Timeline
Striped muscle and tendon Sensory nerve endings Motor nerve endings Human (approximate age) weeks Chick (Tello) (approximate age) days
Beginning differentiation 7 5
Myofibrils appear Exploratory fibres with bulbous endings penetrate into muscles 8 6
Great increase of connective tissue. Vast numbers of nuclei - - - 6-7
Isolated “fat” fibres - 10-12 7
Varicose endings in contact with myotubes - 10
Tendon fibres diflerentiate 12 10
Beginning pacinian corpuscle 20 11
Multiplication of myotubes - 12-22 9-13
Spindles differentiate - 20 12
Dissociation of myotubes from one another. Nuclei become peripheral Spindles become complex 22-26 13
pacinian corpuscle well developed 26-28 15
Plates begin to differentiate 26-28 (very rudimentary except tongue) 18
Data: Hewer (1935)[35] (human weeks appear to be fertilization age based on CRL)   Links: timeline | chicken | skeletal muscle

Tongue

Fetal Tongue Circumference
Fertilisation Age
(weeks)
Gestational Age
GA (weeks)
Mean Circumference
(mm)
12 14 28
13 15 33
14 16 36
15 17 37
16 18 43
17 19 48
18 20 51
19 21 55
20 22 58
21 23 62
22 24 64
23 25 70
24 26 73
Table data[60] Tongue circumference measured by transvaginal ultrasonography between 14 and 17 GA weeks, and by abdominal ultrasound between 18 and 26 GA weeks of gestation.
Links: tongue | fetal | ultrasound

Tooth

Human Dentition Timeline
Milk Dentition
Median incisors 6th to 8th month
Lateral incisors 8th to 12th month
First molars 12th to 16th month
Canines 1 7th to 20th month
Second molars 20th to 24th month
Permanent Dentition
First molars 7th year
Median incisors 8th year
Lateral incisors 9th year
First premolars 10th year
Second premolars 11th year
Canines 13th to 14th year
Second molars 13th to 14th year
Third molars 17th to 40th year
Approximate timings only, vary considerably according to racial, climatic, and nutritive conditions.
Data source: Keibel and Mall (1912)[61] The teeth

    Links: tooth

Integumentary

Human Embryonic Eyelid Timeline
Carnegie Stage Event
10 optic primordia appear
13 By the end of the fourth week the optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode.
14 (about 32 days) the lens placode is indented by the lens pit.
15 (about 33 days) the lens pit is closed. The lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface.
16 (37 days) Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it.
17 - 19 grooves deepen, eyelid folds develop, first below, and then above, the eye.
19 - 22 eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19.
20 the inner canthus is established.
23 closure of the eyelids is complete (Note - shown as still open in some Kyoto embryo).
Data - from Kyoto embryos with Carnegie staging.[7]   Links: eyelid


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