Musculoskeletal System Development

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Introduction

Mesoderm (week 4)
Developing muscle, cartilage and bone.

The mesoderm forms nearly all the connective tissues of the musculoskeletal system. Each tissue (cartilage, bone, and muscle) goes through many different mechanisms of differentiation.

The musculoskeletal system consists of skeletal muscle, bone, and cartilage and is mainly mesoderm in origin with some neural crest contribution.

The intraembryonic mesoderm can be broken into paraxial, intermediate and lateral mesoderm relative to its midline position. During the 3rd week the paraxial mesoderm undergoes somitogenesis and forms into paired "balls" of somites either side of the neural groove.

Somites appear bilaterally as pairs at the same time and form earliest at the cranial (rostral,brain) end of the neural groove and add sequentially at the caudal end. This addition occurs so regularly that embryos are staged according to the number of somites that are present. Different regions of the somite differentiate into dermomyotome (dermal and muscle component) and sclerotome (forms vertebral column). An example of a specialized musculoskeletal structure can be seen in the development of the limbs.

Skeletal muscle forms by fusion of mononucleated myoblasts to form mutinucleated myotubes. Bone is formed through a lengthy process involving ossification of a cartilage formed from mesenchyme. Two main forms of ossification occur in different bones, intramembranous (eg skull) and endochondrial (eg limb long bones) ossification. Ossification continues postnatally, through puberty until mid 20s. Early ossification occurs at the ends of long bones.

Musculoskeletal and limb abnormalities are one of the largest groups of congenital abnormalities.


Musculoskeletal Links: Introduction | mesoderm | somitogenesis | limb | cartilage | bone | bone timeline | bone marrow | shoulder | pelvis | axial skeleton | skull | joint | skeletal muscle | muscle timeline | tendon | diaphragm | Lecture - Musculoskeletal | Lecture Movie | musculoskeletal abnormalities | limb abnormalities | developmental hip dysplasia | cartilage histology | bone histology | Skeletal Muscle Histology | Category:Musculoskeletal
Historic Embryology - Musculoskeletal  
1853 Bone | 1885 Sphenoid | 1902 - Pubo-femoral Region | Spinal Column and Back | Body Segmentation | Cranium | Body Wall, Ribs, and Sternum | Limbs | 1901 - Limbs | 1902 - Arm Development | 1906 Human Embryo Ossification | 1906 Lower limb Nerves and Muscle | 1907 - Muscular System | Skeleton and Limbs | 1908 Vertebra | 1908 Cervical Vertebra | 1909 Mandible | 1910 - Skeleton and Connective Tissues | Muscular System | Coelom and Diaphragm | 1913 Clavicle | 1920 Clavicle | 1921 - External body form | Connective tissues and skeletal | Muscular | Diaphragm | 1929 Rat Somite | 1932 Pelvis | 1940 Synovial Joints | 1943 Human Embryonic, Fetal and Circumnatal Skeleton | 1947 Joints | 1949 Cartilage and Bone | 1957 Chondrification Hands and Feet | 1968 Knee

Some Recent Findings

  • Cell-matrix signals specify bone endothelial cells during developmental osteogenesis[1] “Blood vessels in the mammalian skeletal system control bone formation and support haematopoiesis by generating local niche environments. Here, we report that embryonic and early postnatal long bone contains a specialized endothelial cell subtype, termed type E, which strongly supports osteoblast lineage cells and later gives rise to other endothelial cell subpopulations. The differentiation and functional properties of bone endothelial cells require cell-matrix signalling interactions." bone | blood vessel
More recent papers  
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Search term: Musculoskeletal Development | Musculoskeletal Embryology

Stage20-23 limbs b.jpg Fetal head lateral.jpg

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Vertebrate segmentation: from cyclic gene networks to scoliosis[2] "One of the most striking features of the human vertebral column is its periodic organization along the anterior-posterior axis. This pattern is established when segments of vertebrates, called somites, bud off at a defined pace from the anterior tip of the embryo's presomitic mesoderm (PSM). To trigger this rhythmic production of somites, three major signaling pathways--Notch, Wnt/β-catenin, and fibroblast growth factor (FGF)--integrate into a molecular network that generates a traveling wave of gene expression along the embryonic axis, called the "segmentation clock." Recent systems approaches have begun identifying specific signaling circuits within the network that set the pace of the oscillations, synchronize gene expression cycles in neighboring cells, and contribute to the robustness and bilateral symmetry of somite formation. These findings establish a new model for vertebrate segmentation and provide a conceptual framework to explain human diseases of the spine, such as congenital scoliosis."

Textbooks

Logo.png Hill, M.A. (2020). UNSW Embryology (20th ed.) Retrieved March 19, 2024, from https://embryology.med.unsw.edu.au
Musculoskeletal Links: Introduction | mesoderm | somitogenesis | limb | cartilage | bone | bone timeline | bone marrow | shoulder | pelvis | axial skeleton | skull | joint | skeletal muscle | muscle timeline | tendon | diaphragm | Lecture - Musculoskeletal | Lecture Movie | musculoskeletal abnormalities | limb abnormalities | developmental hip dysplasia | cartilage histology | bone histology | Skeletal Muscle Histology | Category:Musculoskeletal
Historic Embryology - Musculoskeletal  
1853 Bone | 1885 Sphenoid | 1902 - Pubo-femoral Region | Spinal Column and Back | Body Segmentation | Cranium | Body Wall, Ribs, and Sternum | Limbs | 1901 - Limbs | 1902 - Arm Development | 1906 Human Embryo Ossification | 1906 Lower limb Nerves and Muscle | 1907 - Muscular System | Skeleton and Limbs | 1908 Vertebra | 1908 Cervical Vertebra | 1909 Mandible | 1910 - Skeleton and Connective Tissues | Muscular System | Coelom and Diaphragm | 1913 Clavicle | 1920 Clavicle | 1921 - External body form | Connective tissues and skeletal | Muscular | Diaphragm | 1929 Rat Somite | 1932 Pelvis | 1940 Synovial Joints | 1943 Human Embryonic, Fetal and Circumnatal Skeleton | 1947 Joints | 1949 Cartilage and Bone | 1957 Chondrification Hands and Feet | 1968 Knee
The Developing Human, 8th edn.jpg Moore, K.L. & Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders.
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.
Earlier Textbooks
  • The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter 15 the skeletal system
  • Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 11 Limb Dev (bone not well covered in this textbook)
  • Before we Are Born (5th ed.) Moore and Persaud Chapter 16,17: p379-397, 399-405
  • Essentials of Human Embryology Larson Chapter 11 p207-228

Objectives

  • Identify the components of a somite and the adult derivatives of each component.
  • Give examples of sites of endochondral and intramembranous ossification and to compare these two processes.
  • Identify the general times of formation of primary and of formation of secondary ossification centres, and of fusion of such centres with each other.
  • Briefly summarise the development of the limbs.
  • Describe the developmental abnormalities responsible for the following malformations: selected growth plate disorders; congenital dislocation of the hip; scoliosis; arthrogryposis; and limb reduction deformities.

Development Overview

Bone is a connective tissue and develops from mesoderm except in the head where neural crest also contributes. Below is a very brief cartoon overview using simple figures of 3 aspects of early musculoskeletal development. More detailed overviews are shown on other notes pages Mesoderm and Somite, Vertebral Column, Limb in combination with serial sections and Carnegie images.

Mesoderm Development

Mesoderm cartoon 01.jpg Cells migrate through the primitive streak to form mesodermal layer. Extraembryonic mesoderm lies adjacent to the trilaminar embryo totally enclosing the amnion, yolk sac and forming the connecting stalk.
Mesoderm cartoon 02.jpg Paraxial mesoderm accumulates under the neural plate with thinner mesoderm laterally. This forms 2 thickened streaks running the length of the embryonic disc along the rostrocaudal axis. In humans, during the 3rd week, this mesoderm begins to segment. The neural plate folds to form a neural groove and folds.
Mesoderm cartoon 03.jpg Segmentation of the paraxial mesoderm into somites continues caudally at 1 somite/90minutes and a cavity (intraembryonic coelom) forms in the lateral plate mesoderm separating somatic and splanchnic mesoderm.

Note intraembryonic coelomic cavity communicates with extraembryonic coelom through portals (holes) initially on lateral margin of embryonic disc.

Mesoderm cartoon 04.jpg Somites continue to form. The neural groove fuses dorsally to form a tube at the level of the 4th somite and "zips up cranially and caudally and the neural crest migrates into the mesoderm.

Somite Development

Somite cartoon1.png Mesoderm beside the notochord (axial mesoderm, blue) thickens, forming the paraxial mesoderm as a pair of strips along the rostro-caudal axis.
Somite cartoon2.png Paraxial mesoderm towards the rostral end, begins to segment forming the first somite. Somites are then sequentially added caudally. The somitocoel, is a cavity forming in early somites, which is lost as the somite matures.
Somite cartoon3.png Cells in the somite differentiate medially to form the sclerotome (forms vertebral column) and dorsolaterally to form the dermomyotome.
Somite cartoon4.png The dermomyotome then forms the dermotome (forms dermis) and myotome (forms muscle).

Neural crest cells migrate beside and through somite.

Somite cartoon5.png The myotome differentiates to form 2 components dorsally the epimere and ventrally the hypomere, which in turn form epaxial and hypaxial muscles respectively. The bulk of the trunk and limb muscle coming from the Hypaxial mesoderm. Different structures will be contributed depending upon the somite level.

Somite Links: 1 paraxial | 2 early somite | 3 sclerotome and dermomyotome | 4 dermatome and myotome | 5 somite spreading | SEM image - Human Embryo (week 4) showing somites | Movie - somitogenesis Hes expression


Limb Development

Mesoderm cartoon 09.jpg Mesoderm within the developing limb bud differentiates to initially form cartilage which later ossifies by endochondral ossification.

Hypaxial somitic mesoderm from somites at the levels of limb bud formation, migrates into the bud. These cells within the bud proliferate in regions of muscle formation, fuse to form myotubes and then differentiate to form skeletal muscle cells.

Shoulder and Pelvis

Hip bone

The skeletal shoulder consists of: the clavicle (collarbone), the scapula (shoulder blade), and the humerus. Development of his region occurs through both forms of ossification processes.

The skeletal pelvis consists of: the sacrum and coccyx (axial skeleton), and pelvic girdle formed by a pair of hip bones (appendicular skeleton). Before puberty, he pelvic girdle also consists of three unfused bones: the ilium, ischium, and pubis. In chicken, the entire pelvic girdle originates from the somatopleure mesoderm (somite levels 26 to 35) and the ilium, but not of the pubis and ischium, depends on somitic and ectodermal signals.[3]


Links: Shoulder Development | Pelvis Development

Sternum

For details on sternum development see axial skeleton notes. The sternum and sternal ribs derive from the somatic layer of the lateral plate mesoderm.[4][5]

Links: sternum

References

  1. Langen UH, Pitulescu ME, Kim JM, Enriquez-Gasca R, Sivaraj KK, Kusumbe AP, Singh A, Di Russo J, Bixel MG, Zhou B, Sorokin L, Vaquerizas JM & Adams RH. (2017). Cell-matrix signals specify bone endothelial cells during developmental osteogenesis. Nat. Cell Biol. , 19, 189-201. PMID: 28218908 DOI.
  2. Pourquié O. (2011). Vertebrate segmentation: from cyclic gene networks to scoliosis. Cell , 145, 650-63. PMID: 21620133 DOI.
  3. Malashichev Y, Christ B & Pröls F. (2008). Avian pelvis originates from lateral plate mesoderm and its development requires signals from both ectoderm and paraxial mesoderm. Cell Tissue Res. , 331, 595-604. PMID: 18087724 DOI.
  4. Sadler TW. (2000). Embryology of the sternum. Chest Surg. Clin. N. Am. , 10, 237-44, v. PMID: 10803330
  5. Mekonen HK, Hikspoors JP, Mommen G, Köhler SE & Lamers WH. (2015). Development of the ventral body wall in the human embryo. J. Anat. , 227, 673-85. PMID: 26467243 DOI.


Online Textbooks

Reviews

Pourquié O. (2011). Vertebrate segmentation: from cyclic gene networks to scoliosis. Cell , 145, 650-63. PMID: 21620133 DOI.

Piróg KA & Briggs MD. (2010). Skeletal dysplasias associated with mild myopathy-a clinical and molecular review. J. Biomed. Biotechnol. , 2010, 686457. PMID: 20508815 DOI.

Sayer AA & Cooper C. (2005). Fetal programming of body composition and musculoskeletal development. Early Hum. Dev. , 81, 735-44. PMID: 16081228 DOI.

Walker JM. (1991). Musculoskeletal development: a review. Phys Ther , 71, 878-89. PMID: 1946622

Articles

Applegate KE. (2004). Can MR imaging be used to characterize fetal musculoskeletal development?. Radiology , 233, 305-6. PMID: 15516609 DOI.

Ryu JK, Cho JY & Choi JS. (2003). Prenatal sonographic diagnosis of focal musculoskeletal anomalies. Korean J Radiol , 4, 243-51. PMID: 14726642 DOI.

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Cite this page: Hill, M.A. (2024, March 19) Embryology Musculoskeletal System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Musculoskeletal_System_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G