BGDA Lecture - Development of the Embryo/Fetus 2

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Introduction

Human development timeline graph 02.jpg

Activity: Lecture Title: Development of the embryo/fetus 2 Scheduled:

This lecture covers the period of Embryonic development, in Humans from week 3 to week 8 and is divided into 23 Carnegie stages of embryonic development. There will also be a brief introduction to fetal development. Note, the period from week 9 to week 38 is considered Fetal development and will be covered in detail in the Laboratory 12.

  • Embryonic Development
  • Organ and System formation (Functioning / Not Functional)
  • Dynamic changes internal and external
  • Carnegie stages illustrate external development
Currently being updated for 2014 (this notice removed when completed).


Lecture Archive: 2013 | 2012 | 2010 | 2008

Textbooks

Logo.png Hill, M.A. (2014). UNSW Embryology (14th ed.) Retrieved April 24, 2014, from http://php.med.unsw.edu.au/embryology
The Developing Human, 9th edn.jpg Moore, K.L; Persaud, T.V.N; Torchia, M.G. The Developing Human : Clinically Oriented Embryology 8th ed. Philadelphia, PA : Saunders/Elsevier, c2011. (links only function with UNSW connection)
Larsen's human embryology 4th edn.jpg Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. and Francis-West, P.H. (2009). Larsen’s Human Embryology (4th ed.). New York; Edinburgh: Churchill Livingstone.


First 8 Weeks

Human Carnegie stage 1-23.jpg

The Carnegie stages of the first 8 week of human development.

Week 3

Week 3 - Gastrulation

Mesoderm means the "middle layer" and it is from this layer that nearly all the bodies connective tissues are derived. In early mesoderm development a number of transient structures will form and then be lost as tissue structure is patterned and organised. Humans are vertebrates, with a "backbone", and the first mesoderm structure we will see form after the notochord will be somites.

Facts: Week 4, 22 - 23 days, 2 - 3.5 mm, Somite Number 4 - 12

View: This is a dorsal view of the human embryo, the amniotic membrane has been removed. Top embryo is an early stage 10, bottom is late stage 10.

Mesoderm organization: lateral plate - intermediate mesoderm - paraxial mesoderm - axial mesoderm - paraxial mesoderm - intermediate mesoderm - lateral plate

Axial Mesoderm

  • notochord
  1. mechanical role in embryonic disc folding
  2. molecular role in patterning surrounding tissues

Adult - contributes to the nucleus pulposis of the intervertebral disc

Paraxial Mesoderm

Stage 7 paraxial mesoderm
  • differentiates rostro-caudally (head to tail)
  • remains unsegmented in the head region.
  • segments in the body region to form pairs of somites along the length of the embryo.

Adult - contributes vertebral column (vertebra and IVD), dermis of the skin, skeletal muscle of body and limbs

Intermediate Mesoderm

Stage 7 intermediate mesoderm
  • named by position (between paraxial and lateral plate)
  • differentiates rostro-caudally (head to tail)
  • forms 3 sets of "kidneys" in sequence
  1. pronephros
  2. mesonephros
  3. metanephros

Adult - metanephros forms the kidney

Lateral Plate Mesoderm

Stage 7 lateral plate
  • a "horseshoe shaped" space forms in the middle
  • somatic mesoderm - closest to ectoderm
  • space - forms the 3 body cavities (pericardial, pleural, peritoneal)
  • splanchnic mesoderm - closest to endoderm

Adult - body connective tissues, gastrointestinal tract (connective tissues, muscle, organs), heart

Somite Development

Stage11 sem100.jpg

Section through Embryo (Stage 11)

Somite initially forms 2 main components

  • ventromedial- sclerotome forms vertebral body and intervertebral disc
  • dorsolateral - dermomyotome forms dermis and skeletal muscle

Sclerotome

  • sclerotome later becomes subdivided
    • rostral and caudal halves separated laterally by von Ebner's fissure
  • half somites contribute to a single vertebral level body
  • other half intervertebral disc
  • therefore final vertebral segmentation “shifts”

Myotome

  • Body - epaxial and hypaxial muscles
  • Limbs - flexor and extensor muscles

Dermatome

  • connective tissue underlying epidermis
  • begins as a dorsal thickening
  • spreads throughout the body

Mesoderm 001 icon.jpg Somite 001 icon.jpg Vertabra 003 icon.jpg

Week 4

Heart

Week3 folding icon.jpg
 ‎‎Week 3
Page | Play
Heart1 looping icon.jpg
 ‎‎Heart Looping
Page | Play
Heart1 realign icon.jpg
 ‎‎Heart Realign
Page | Play
Heart1 atrium icon.jpg
 ‎‎Atrial Septation
Page | Play
Heart1 ventricle icon.jpg
 ‎‎Outflow Septation
Page | Play
Stage 7 lateral plate

Heart Looping Sequence (SEMs).jpg

Mesoderm vascular development
  • forms initially in splanchnic mesoderm of prechordal plate region - cardiogenic region
    • growth and folding of the embryo moves heart ventrallly and downward into anatomical position
  • week 3 begins as paired heart tubes that fuse to form single heart tube
  • begins to beat in Humans- day 22-23
  • heart tube connects to blood vessels forming in splanchnic and extraembryonic mesoderm

Week 2-3 pair of thin -walled tubes

Week 3 tubes fused, truncus arteriosus outflow, heart contracting

Week 4 heart tube continues to elongate, curving to form S shape

Week 5 Septation starts, atrial and ventricular

Septation continues, atrial septa remains open, foramen ovale

Links: Cardiac Embryology

Neural

Stage 10 Week 4, 22 - 23 days
Stage 11 neural groove to tube

Neural Plate

Neuralplate cartoon.png

Neuralplate 001 icon.jpg

  • extends from buccopharyngeal membrane to primitive node
  • forms above notochord and paraxial mesoderm
  • neuroectodermal cells
    • broad brain plate
    • narrower spinal cord
  • 3 components form: floor plate, neural plate, neural crest

Neural Groove

  • forms in the midline of the neural plate (day 18-19)
  • either side of which are the neural folds which continues to deepen until about week 4
  • neural folds begins to fuse, beginning at 4th somite level

Neural Tube

Stage 12 caudal neuropore Neuraltube 001 icon.jpg

  • the neural tube forms the brain and spinal cord
  • fusion of neural groove extends rostrally and caudally
  • begins at the level of 4th somite
  • closes neural groove "zips up" in some species.
    • humans appear to close at multiple points along the tube.
  • leaves 2 openings at either end - Neuropores
    • cranial neuropore closes before caudal

Failure for the neural tube to close correctly or completely results in a neural tube defect.

Neural Crest

  • population of cells at the edge of the neural plate that lie dorsally when the neural tube fuses
  • dorsal to the neural tube, as a pair of streaks
  • pluripotential, forms many different types of cells
  • cells migrate throughout the embryo

Neural Crest Derivatives: dorsal root ganglia, autonomic ganglia, adrenal medulla, drg sheath cells, glia, pia-arachnoid sheath, skin melanocytes, connective tissue of cardiac outflow, thyroid parafollicular cells, craniofacial skeleton, teeth odontoblasts

Head

Stage 14 pharyngeal arches
  • branchial arch (Gk. branchia= gill)
  • arch consists of all 3 trilaminar embryo layers (ectoderm- outside, mesoderm - core of mesenchyme, endoderm - inside)
  • Humans have 5 arches - 1, 2, 3, 4, 6 (Arch 5 does not form or regresses rapidly)
  • from in rostro-caudal sequence, Arch 1 to 6 from week 4 onwards
  • arch 1 and 2 appear at time of closure of cranial neuropore
  • Face - mainly arch 1 and 2
  • Neck components - arch 3 and 4 (arch 4 and 6 fuse)

Face 001 icon.jpg

Sensory Placodes

  • During week 4 a series of thickened surface ectodermal patches form in pairs rostro-caudally in the head region.
  • These sensory placodes will later contribute key components of each of our special senses (vision, hearing and smell).
  • Note that their initial postion on the developing head is significantly different to their final position in the future sensory system
  • Otic placode - istage 13/14 embryo the otic placode sunk from the surface ectoderm to form a hollow epithelial ball, the otocyst, which now lies beneath the surface surrounded by mesenchyme (mesoderm). The epithelia of this ball varies in thickness and has begun to distort, it will eventually form the inner ear membranous labyrinth.
  • Lens placode - lies on the surface, adjacent to the outpocketing of the nervous system (which will for the retina) and will form the lens.
  • Nasal placode - has 2 components (medial and lateral) and will form the nose olefactory epithelium.

Upper and Lower Limb

Stage14 somites limbbuds.png
  • Limb development occurs at different times for forelimbs and hindlimbs.
  • mid-4th week human upper limb buds first
  • lower limbs about 2 days later
  • The limbs form at vertebra segmental levels C5-C8 (upper limbs) L3-L5 (lower limbs).
  • Limbs are initially undifferentiated mesenchyme (mesoderm) with an epithelial (ectoderm) covering.
  • Blood vessels then begin forming, the largest (marginal vein) is adjacent to tip of the bud.
  • Myotome invade the bud.

Gastrointestinal Tract

  • Begins at buccopharyngeal membrane
  • Ends at cloacal membrane
  • 3 distinct portions (fore-, mid- and hind-gut)
  • liver earliest forming organ

Germ layer contributions

  • Endoderm - epithelium and associated glands
  • Mesoderm (splanchnic) - mesentry, connective tissues, smooth muscle, blood vessels
  • Ectoderm (neural crest) - enteric nervous system

Both endoderm and mesoderm will contribute to associated organs.

Week 5

Stage 14 pharyngeal arches
  • Heart - septation starts, atrial and ventricular
  • Vascular - 3 vascular systems (systemic, placental, vitelline) extensively remodelled
  • Respiratory - left and right lung buds push into the pericardioperitoneal canals (primordia of pleural cavity)
  • Sense - Hearing cochlear part of otic vesicle elongates (humans 2.5 turns)

Week 6

Week 6 Face Development
  • Endocrine development
    • Pituitary - connecting stalk between pouch and oral cavity degenerates
    • Parathyroid - diverticulum elongate, hollow then solid, dorsal cell proliferation
    • Thymus - diverticulum elongate, hollow then solid, ventral cell proliferation
    • Adrenal - fetal cortex forms from mesothelium adjacent to dorsal mesentery, medulla neural crest cells from adjacent sympathetic ganglia

Week 7

Human week 7
  • Pancreas - Week 7 to 20 pancreatic hormones secretion increases, small amount maternal insulin
  • Limb bones form by endochondrial ossification and throughout embryo replacement of cartilage with bone (week 5 onward).

Week 8

  • Limb upper and lower limbs rotate in different directions (upper limb dorsally, lower limb ventrally)

Stage20-23 limbs a.jpg


Links: Embryonic Development | Timeline human development

Fetal

Fetal length and weight changes
  • First Trimester (1 - 12 weeks) - embryonic and early fetal
  • Second Trimester (13 - 24 weeks) - organ development and function, growth (length)
  • Third Trimester (25 - 40 weeks) - organ function and rapid growth (weight)

Fetal Neural

Timeline of events in Human Neural Development
  • During the fetal period there is ongoing growth in size, weight and surface area of the brain and spinal cord. Microscopically there is ongoing: cell migration, extension of processes, cell death and glial cell development.
  • Brain - Insular cortex, Gyral and Sulcal development
  • Neural development will continue after birth with substantial growth, death and reorganization occuring during the postnatal period

Lung Stages

  • week 4 - 5 embryonic
  • week 5 - 17 pseudoglandular
  • week 16 - 25 canalicular
  • week 24 - 40 terminal sac
  • late fetal - 8 years alveolar

Fetal Genital

  • ovary and testis development
  • external genital development
  • testis descent

Fetal Renal

  • week 32-34 nephron development completed
  • term birth nephron number per kidney about 1 million (300,000 to 2 million)

Fetal Endocrine

  • Pituitary Hormones - HPA axis established by week 20, pituitary functional throughout fetal development
  • Thyroid Hormone - important for neural development, required for metabolic activity, also in the newborn

Remember that the Placenta also has important endocrine functions during development.

Critical Periods

The term "Critical Periods" refers to periods of development when specific systems are more sensitive to teratogen exposure or developmental insults.

Human-critical periods of development.jpg
Conceptus Embryonic development (weeks) Fetal period (weeks)
1
2
3
4
5
6
7
8
9
16
20-36
38
Early zygote.jpg Week2 001 icon.jpg Stage9 sem4c.jpg Stage13 sem1c.jpg Stage15 bf1c.jpg Stage17 bf1c.jpg Stage19 bf1c.jpg Stage23 bf1c.jpg
Neural
Stage2.jpg Heart
Upper limbs
Lower limbs
Ear
Eye
CSt3.jpg Palate
Teeth
Week2 001 icon.jpg External genitalia
Loss Major abnormalities Functional and Minor abnormalities

Next


Carnegie Stage Table

Weeks shown in the table below are embryonic post ovulation age, for clinical Gestational Age (GA) measured from last menstrual period, add 2 weeks.

Stage
Days (approx)
Size
(mm)
Images
(not to scale)
Events
1
1
(week 1)
0.1 - 0.15
Human zygote two pronuclei 02.jpg
fertilized oocyte, zygote, pronuclei
2
2 - 3
0.1 - 0.2
Human embryo day 3.jpg
morula cell division with reduction in cytoplasmic volume, blastocyst formation of inner and outer cell mass
3
4 - 5
0.1 - 0.2
Human embryo day 5.jpg
loss of zona pellucida, free blastocyst
4
5 - 6
0.1 - 0.2
Week2 001 icon.jpg
attaching blastocyst
5
7 - 12
(week 2)
0.1 - 0.2
Stage5 bf11L.jpg
implantation
6
13 - 15
0.2
Stage6 bf03.jpg
extraembryonic mesoderm, primitive streak, gastrulation
7
15 - 17
(week 3)
0.4
Stage7 features.jpg
gastrulation, notochordal process
8
17 - 19
1.0 - 1.5
Stage8 bf4.jpg
primitive pit, notochordal canal
9
19 - 21
1.5 - 2.5
Stage9 dorsal.jpg
Somitogenesis Somite Number 1 - 3 neural folds, cardiac primordium, head fold
10
22 - 23
(week 4)
2 - 3.5
Stage10 bf4b.jpg
Somite Number 4 - 12 neural fold fuses
11
23 - 26
2.5 - 4.5
Stage11 bf7b.jpg
Somite Number 13 - 20 rostral neuropore closes
12
26 - 30
3 - 5
Stage12 bf5b.jpg
Somite Number 21 - 29 caudal neuropore closes
13
28 - 32
(week 5)
4 - 6
Stage13 bf2c.jpg
Somite Number 30 leg buds, lens placode, pharyngeal arches
Stage 13/14 shown in serial embryo sections series of Embryology Program
14
31 - 35
5 - 7
Stage14 bf2c.jpg
lens pit, optic cup
15
35 - 38
7 - 9
Stage15 bf1c.jpg
lens vesicle, nasal pit, hand plate
16
37 - 42
(week 6)
8 - 11
Link=Carnegie_stage_16
nasal pits moved ventrally, auricular hillocks, foot plate
17
42 - 44
11 - 14
Stage17 bf1c.jpg
finger rays
18
44 - 48
(week 7)
13 - 17
Stage18 bf1c.jpg
ossification commences
19
48 - 51
16 - 18
Stage19 bf1c.jpg
straightening of trunk
20
51 - 53
(week 8)
18 - 22
Stage20 bf1c.jpg
upper limbs longer and bent at elbow
21
53 - 54
22 - 24
Stage21 bf1c.jpg
hands and feet turned inward
Stage 22 shown in serial embryo sections series of Embryology Program
22
54 - 56
23 - 28
Stage22 bf1c.jpg
eyelids, external ears
23
56 - 60
27 - 31
Stage23 bf1c.jpg
rounded head, body and limbs
Following this stage Fetal Development occurs until birth (approx 37 weeks)

The embryos shown in the table are from the Kyoto and Carnegie collection and other sources.


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Cite this page: Hill, M.A. (2014) Embryology BGDA Lecture - Development of the Embryo/Fetus 2. Retrieved April 24, 2014, from http://embryology.med.unsw.edu.au/embryology/index.php?title=BGDA_Lecture_-_Development_of_the_Embryo/Fetus_2

What Links Here?
Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
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