Musculoskeletal System Development

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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 forms into "balls" of mesoderm paired either side of the neural groove, called somites.

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 | Axial Skeleton | Skull | Joint | Muscle | Tendon | Diaphragm | Lecture - Musculoskeletal Development | Abnormalities | Limb Abnormalities | Cartilage Histology | Bone Histology | Skeletal Muscle Histology | Category:Musculoskeletal

Some Recent Findings

  • Developmental Dynamics - Special Issue: Special Issue on Limb Development May 2011 Volume 240, Issue 5
  • Vertebrate segmentation: from cyclic gene networks to scoliosis[1] "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."
More recent papers
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This table shows an automated computer PubMed search using the listed sub-heading term.
  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent

Search term: Musculoskeletal Development

Heather Paxton, Peter G Tickle, Jeffery W Rankin, Jonathan R Codd, John R Hutchinson Anatomical and biomechanical traits of broiler chickens across ontogeny. Part II. Body segment inertial properties and muscle architecture of the pelvic limb. PeerJ: 2014, 2;e473 PMID:25071996 Peter G Tickle, Heather Paxton, Jeffery W Rankin, John R Hutchinson, Jonathan R Codd Anatomical and biomechanical traits of broiler chickens across ontogeny. Part I. Anatomy of the musculoskeletal respiratory apparatus and changes in organ size. PeerJ: 2014, 2;e432 PMID:25071981 A Giusti, G Bianchi Male osteoporosis. Reumatismo: 2014, 66(2);136-43 PMID:25069495 Tomoyuki Suzuki, Konsei Shino, Hidenori Otsubo, Daisuke Suzuki, Tatsuo Mae, Mineko Fujimiya, Toshihiko Yamashita, Hiromichi Fujie Biomechanical Comparison Between the Rectangular-Tunnel and the Round-Tunnel Anterior Cruciate Ligament Reconstruction Procedures With a Bone-Patellar Tendon-Bone Graft. Arthroscopy: 2014; PMID:25064752 Andrew J Muir, Sanjeev Arora, Gregory Everson, Robert Flisiak, Jacob George, Reem Ghalib, Stuart C Gordon, Todd Gray, Susan Greenbloom, Tarek Hassanein, Jan Hillson, Maria Arantxa Horga, Ira M Jacobson, Lennox Jeffers, Kris V Kowdley, Eric Lawitz, Stefan Lueth, Maribel Rodriguez-Torres, Vinod Rustgi, Lynn Shemanski, Mitchell L Shiffman, Subasree Srinivasan, Hugo E Vargas, John M Vierling, Dong Xu, Juan C Lopez-Talavera, Stefan Zeuzem, for the EMERGE study group A Randomized Phase 2b Study of Peginterferon Lambda-1a for the Treatment of Chronic HCV Infection. J. Hepatol.: 2014; PMID:25064437

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


Logo.png Hill, M.A. (2014). UNSW Embryology (14th ed.) Retrieved July 30, 2014, from
Musculoskeletal Links: Introduction | Mesoderm | Somitogenesis | Limb | Cartilage | Bone | Bone Timeline | Axial Skeleton | Skull | Joint | Muscle | Tendon | Diaphragm | Lecture - Musculoskeletal Development | Abnormalities | Limb Abnormalities | Cartilage Histology | Bone Histology | Skeletal Muscle Histology | Category:Musculoskeletal
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


  • 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

Mesoderm cartoon 05.jpg Mesoderm beside the notochord (axial mesoderm, blue) thickens, forming the paraxial mesoderm as a pair of strips along the rostro-caudal axis.
Mesoderm cartoon 06.jpg 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.
Mesoderm cartoon 07.jpg Cells in the somite differentiate medially to form the sclerotome (forms vertebral column) and dorsolaterally to form the dermomyotome.
Mesoderm cartoon 08.jpg The dermomyotome then forms the dermotome (forms dermis) and myotome (forms muscle).

Neural crest cells migrate beside and through somite.

Mesoderm cartoon 09.jpg 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.

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.[2]

Links: Shoulder Development | Pelvis Development


  1. Olivier Pourquié Vertebrate segmentation: from cyclic gene networks to scoliosis. Cell: 2011, 145(5);650-63 PMID:21620133
  2. Yegor Malashichev, Bodo Christ, Felicitas Pröls Avian pelvis originates from lateral plate mesoderm and its development requires signals from both ectoderm and paraxial mesoderm. Cell Tissue Res.: 2008, 331(3);595-604 PMID:18087724

Online Textbooks


Olivier Pourquié Vertebrate segmentation: from cyclic gene networks to scoliosis. Cell: 2011, 145(5);650-63 PMID:21620133

Katarzyna A Piróg, Michael D Briggs Skeletal dysplasias associated with mild myopathy-a clinical and molecular review. J. Biomed. Biotechnol.: 2010, 2010;686457 PMID:20508815

Avan Aihie Sayer, Cyrus Cooper Fetal programming of body composition and musculoskeletal development. Early Hum. Dev.: 2005, 81(9);735-44 PMID:16081228

J M Walker Musculoskeletal development: a review. Phys Ther: 1991, 71(12);878-89 PMID:1946622


Kimberly E Applegate Can MR imaging be used to characterize fetal musculoskeletal development? Radiology: 2004, 233(2);305-6 PMID:15516609

Jung Kyu Ryu, Jeong Yeon Cho, Jong Sun Choi Prenatal sonographic diagnosis of focal musculoskeletal anomalies. Korean J Radiol: 2004, 4(4);243-51 PMID:14726642

Search PubMed

Search April 2010

  • Musculoskeletal Development - All (44637) Review (5065) Free Full Text (6601)

Search Pubmed: Musculoskeletal System Development | Musculoskeletal Development

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Cite this page: Hill, M.A. (2014) Embryology Musculoskeletal System Development. Retrieved July 30, 2014, from //

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