Difference between revisions of "Talk:Musculoskeletal System Development"

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Computers with internet access can search from either [#PubMed Below] or directly from [http://www.ncbi.nlm.nih.gov/PubMed/medline.html PubMed Internet Access]  
Computers with internet access can search from either [#PubMed Below] or directly from [http://www.ncbi.nlm.nih.gov/PubMed/medline.html PubMed Internet Access]  
== Glossary of Terms ==
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== Development Terms ==
== Development Terms ==

Revision as of 01:28, 15 April 2010



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.

Human embryo (Stage 10), first forming somites(white "balls" either side of neural groove)
Human embryo (Stage 11), additional somites(paired either side of neural tube)

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. (More? [skmus7.htm limb development])

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 (More? [../Movies/Growth.mov movie mouse ossification]).

Musculoskeletal and limb abnormalities are one of the largest groups of congenital abnormalities. ([skmus2.htm More? see abnormalities])

Page Links: [#Intro Introduction] | [#Recent Some Recent Findings] | [#Reading Reading] | [#Objectives Objectives] | [#Computer Computer Activities] | [#Learn Learning activities] | [#Podcast Podcasts] | [#overview Development Overview] | [#Late Neural Development Late Neural Development] | [#Terms Terms] | [#References References] | [#Glossary Glossary] | [#Terms Development Terms]

Some Recent Findings

Mesoderm - Iimura T, Yang X, Weijer CJ, Pourquie O. Dual mode of paraxial mesoderm formation during chick gastrulation. Proc Natl Acad Sci U S A. 2007 Feb 13; (More? [../Notes/week3_3.htm Week 3 - Gastrulation] | [../OtherEmb/chicken.htm Chicken Development])

"The skeletal muscles and axial skeleton of vertebrates derive from the embryonic paraxial mesoderm. ...fate mapping further shows that the paraxial mesoderm territory in the epiblast is regionalized along the anteroposterior axis as in lower vertebrates. These observations suggest that the mechanisms responsible for paraxial mesoderm formation are largely conserved across vertebrates."

Pattern of Pax7 expression during myogenesis in the posthatch chicken establishes a model for satellite cell differentiation and renewal Orna Halevy etal., Developmental Dynamics (2004) 231:489 - 502


  • Human Embryology (3rd ed.) Larson Ch11 p311-339
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Ch15,16: p405-423, 426-430
  • Before We Are Born (5th ed.) Moore and Persaud Ch16,17: p379-397, 399-405
  • Essentials of Human Embryology Larson Ch11 p207-228
  • Human Embryology, Fitzgerald and Fitzgerald
  • Human Embryology and Developmental Biology, (3rd ed.) Carlson Ch9,10: p173-193, 209-222


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

Computer Activities

UNSW Embryology:

  • [skmus3.htm Carnegie stage 13/14 Embryo Serial Sections (Pig)]
  • [skmus4.htm Carnegie stage 22 Embryo Serial Sections (Human)]
  • [skmus5.htm Selected Carnegie stage 22 Highpower Sections (Human)]
  • [skmus7.htm Limb Development]
  • [skmus8.htm Axial Skeleton Development]
  • [skmus9.htm Bone Development]
  • [skmus8a.htm Skull Development]
  • [../wwwpig/system/PigLimbs.htm Systems- Carnegie stage 13/14 Embryo Serial Sections (Pig)]
  • [../wwwhuman/Stages/stages.htm Human Carnegie stages]
  • Carnegie stage 22 Embryo Grouped Sections (Human) [../wwwhuman/LowSet/ChSet1.htm Body 1], [../wwwhuman/LowSet/ChSet2.htm Body 2], [../wwwhuman/LowSet/AbSet.htm Body 3]), Systems (limbbud) C4-E3,
    These Lecture links are to current and historic courses and may also link directly to PDF version of Lecture slides (educational use only).
  • [../Science/ANAT2341lecture06.htm ANAT2341 (2008) Lecture 6 Mesoderm]
  • [../Sections/anat2300/2004/ANAT2300L06.htm ANAT2300 (2004) Lecture 6 Mesoderm]
  • [../Sections/anat2300/2004/ANAT2300L12.htm ANAT2300 (2004) Lecture 12 Limb]
  • [../Sections/anam1006/2003/week8/lab8.htm ANAM1006 (2003) Musculoskel Development Lab]
  • PDF Documents
  • [../Sections/anat2300/2004/ANAT2310L7Bones1.pdf ANAT2300 (2004) Lecture 7 Bone (view)]
  • [../Sections/anat2300/2004/ANAT2310L7Bones4.pdf ANAT2300 (2004) Lecture 7 Bone (print)]
    • === Human Embryology Movies: ===
  • [../Movies/larsen/somite.mov Fate of the Somite] (315Kb)
  • [../Movies/larsen/vertabr.mov Vertebrae] (366Kb)

Embryo Images Unit:

Body Cavities, Musculoskeletal and Limb Development

Embryo Images Online External links below require Internet connection.

Developmental Biology (6th ed.) Gilbert:

NCBI Bookshelf external links below require Internet connection.


Development Overview

Below is a very brief overview using simple figures of 3 aspects of early musculoskeletal development covering : [#Mesoderm1 Mesoderm] then [#Somite1 Somite] and [#Limb1 Limb] development

More detailed overviews are shown on other notes pages ([skmus6.htm Mesoderm and Somite], [skmus7.htm Vertebral Column], [skmus8.htm Limb]) in combination with serial sections and Carnegie images.

Mesoderm Development

File:Image 001.gif

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.

File:Image 002.gif

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.

File:Image 003.gif

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.

Image 004.gif

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.

Next [#Somite1 Somite Development]

Somite Development

File:Image 005.gif

Mesoderm beside the notochord (axial mesoderm) thickens, forming the paraxial mesoderm as a pair of strips along the rostro-caudal axis.

File:Image 007.gif

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.

File:Image 008.gif

Cells in the somite differentiate medially to form the sclerotome (forms vertebral column) and laterally to form the dermomyotome.

File:Image 009.gif

The dermomyotome then forms the dermotome (forms dermis) and myotome (forms muscle).

Neural crest cells migrate beside and through somite.

File:Image 011.gif

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.

Next section [#Limb1 Limb Development]

Limb Development

Also notes page on [skmus7.htm limb development]

File:Image 011.gif

Carnegie stage 13/14 Embryo Serial Sections (Pig)


Serial section D3 (rotated 90 degrees) Mouseover to identify structures

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.


Note - See also other specific musculoskeletal notes pages: [../Refer/skmus_ref.htm References] | [skmus2#References.htm Abnormalities] | [skmus6#References.htm Somite] | [skmus7#References.htm Limb] | [skmus8#References.htm Axial Skeleton] | [skmus8a#References.htm Skull] | [skmus9#References.htm Bone] | [skmus9a#References.htm Human Bone] | [skmus12#References.htm Skeletal Muscle] | [skmus11#References.htm Molecular]


Baron R, Rawadi G, Roman-Roman S. Wnt signaling: a key regulator of bone mass. Curr Top Dev Biol. 2006;76:103-27.

Pogue R, Lyons K. BMP signaling in the cartilage growth plate. Curr Top Dev Biol. 2006;76:1-48.


Wasteson P, Johansson BR, Jukkola T, Breuer S, Akyürek LM, Partanen J, Lindahl P. Developmental origin of smooth muscle cells in the descending aorta in mice. Development. 2008 May;135(10):1823-32.

Nissim S, Allard P, Bandyopadhyay A, Harfe BD, Tabin CJ. Characterization of a novel ectodermal signaling center regulating Tbx2 and Shh in the vertebrate limb. Dev Biol. 2006 Dec 9;

Search PubMed: Feb 2007 "musculoskeletal development" 35,405 reference articles of which 3,514 were reviews.

Search PubMed Now: musculoskeletal development | mesoderm development

(More? PubMed- Medline)

Selected Lists of References from PubMed March 1999 search results are available for Department of Anatomy computers without internet access: [../Refer/skmus/somitelist.htm Somite Reviews] | [../Refer/skmus/somite.htm Somitogenesis Abstracts] | [../Refer/week2/mesodermrev.htm Mesoderm Review List]

Computers with internet access can search from either [#PubMed Below] or directly from PubMed Internet Access

Development Terms

  • acetabulum-
  • amnion-
  • anlage- (Ger. ) primordium, structure or cells which will form a future structure.
  • annulus fibrosus- the circularly arranged fibers (derived from sclerotome)that together with the nucleus pulposus (derived from notochord) form the [#intervertebral disc intervertebral disc] (IVD) of the vertebral column.
  • apical ectodermal ridge- (=AER) specialized region of ectoderm at the tip of the growing limbbuds that specifies proximo/distal axss of limb development
  • aponeurosis-
  • apoptosis- the process of programmed cell death. In development of the limbs occurs in the "paddle" if both the hand and foot, generating the separated digits. Occurs in many tissues of the embryo and adult.
  • axial mesoderm (=notochord)
  • axillary fossa the future "armpit" region
  • brachial plexus- mixed spinal nerves innervating the upper limb form a complex meshwork (crossing).
  • cartilage- connective tissue from mesoderm in the embryo forms initial skeleton replaced by bone. In adult, found on surface of bone joints.
  • centrum- the primordium of the [#vertebral body vertebral body] formed initially by the sclerotome.
  • clavicle- (L. little key) bone which locks sholder to body.
  • cloacal membrane- at caudal (anal) end of gastrointestinal tract (GIT) where surface ectoderm and GIT endoderm meet forms the openings for GIT, urinary, reproductive tracts. (see also [#buccopharyngeal membrane buccopharyngeal membrane])
  • connective tissue-
  • costotransverse-
  • costovertebral-
  • dermatome-
  • dermomyotome- dorsolateral half of each somite that forms the dermis and muscle.
  • dystrophy-
  • ectoderm- the layer (of the 3 germ cell layers) which form the nervous system from the neural tube and neural crest and also generates the epithelia covering the embryo.
  • ectodermal ring- the thickened ring of ectoderm seen dorsally in the early (stage13/14) embryo adjacent to the dermatome. Ectoderm ventrally is relatively thin, gaining its dermatome component at a later stage.
  • endochondrial ossification- the process of replacement of the cartilagenous framework by osteoblasts with bone.
  • epaxial myotome- the dorsal portion of the myotome that generates dorsal skeletal muscles (epaxial muscles).
  • epimysium-
  • erector spinae-
  • external oblique m.-
  • extracellular matrix- material secreted by and surrounding cells. Consists if fibers and ground substance.
  • ependyma-
  • epiblast- the layer (of the bilaminar embryo) that generates endoderm and mesoderm by migration of cells through the primitive streak. The remaing cells form ectoderm.
  • extensor-
  • fascia-
  • fascicle- (=bundle)
  • femur-
  • fibroblast growth factors- (FGF) a family of at least 10 secreted proteins that bind membrane tyrosine kinase receptors. A patterning switch with many different roles in different tissues. (FGF8 = androgen-induced growth factor (AIGF)
  • fibroblast growth factor receptor- receptors comprise a family of at least 4 related but individually distinct tyrosine kinase receptors (FGFR1- 4). They have a similar protein structure, with 3 immunoglobulin-like domains in the extracellular region, a single membrane spanning segment, and a cytoplasmic tyrosine kinase domain.
  • flexor-
  • fossa-
  • gracilis m.-
  • growth factor- usually a protein or peptide that will bind a cell membrane receptor and then activates an intracellular signaling pathway. The function of the pathway will be to alter the cell directly or indirectly by changing gene expression. (eg shh)
  • hox- (=homeobox) family of transcription factors that bind DNA and activate gene expression. Expression of different Hox genes along neural tube defines rostral-caudal axis and segmental levels.
  • humerus-
  • hypaxial myotome- the ventral portion of the myotome that generates ventral skeletal muscles (hypaxial muscles).
  • inguinal fossa- the region of the lower limb ajacent to flexor surface (exuivilant to the axillary fossa of the upper limb).
  • intercostal- the region between adjacent ribs, usually comprising intercostal muscles and connective tissue.
  • intervertebral disc- (IVD) the annulus fibrosus+nucleus pulposus together form the intervertebral disc (IVD) of the vertebral column. This is the flexible region between each bony vertebra that allows the column to be bent.
  • intervertebral foramina-
  • ischium-
  • lumbar plexus- mixed spinal nerves innervating the lower limb form a complex meshwork (crossing).
  • mesenchyme-
  • mesoderm- the middle layer of the 3 germ cell layers of the embryo. Mesoderm outside the embryo and covering the amnion, yolk and chorion sacs is extraembryonic mesoderm.
  • metacarpal cartilage-
  • muscle- 3 main types of muscle (smooth, cardiac and skeletal) all derived from mesoderm but different regions.
  • myotome-
  • myoblast- the undifferentiated mononucleated muscle cells that will fuse together to form a multinucleated myotube, then mature into a muscle fibre.
  • MyoD- transcription factor involved in the determination of muscle cells in the somite. A basic helix-loop-helix factor which binds DNA.
  • myotome- the portion of the dermamyotome that generates skeletal muscle. Has 2 components epaxial (dorsal muscles ) hypaxial (ventral muscles).
  • neural crest- cell region at edge of neural plate, then atop the neural folds, that remains outside and initially dorsal to the neural tube when it forms. These paired dorsal lateral streaks of cells migrate throughout the embryo and can differentiate into many different cell types(=pluripotential). Those that remain on the dorsal neural tube form the sensory spinal ganglia (DRG). Neural crest cells migrate into the somites.
  • neural tube- neural plate region of ectoderm pinched off to form hollow ectodermal tube above notochord in mesoderm.
  • neuropore- opening at either end of neural tube: cranial=rostral=anterior, caudal=posterior. The cranial neuropore closes (day 25) approx. 2 days (human) before caudal.
  • nucleus pulposus- central region of intervertebral discs of the spinal cord derived from the notochord.
  • notochord- rod of cells lying in mesoderm layer ventral to the neural tube, induces neural tube and secretes sonic hedgehog which "ventralizes" the neural tube and may influence somite development.
  • otocyst- (=otic vesicle) sensory [#placode placode] which sinks into mesoderm to form spherical vesicle (stage 13/14 embryo) that will form components of the inner ear.
  • patella-
  • Pax- name derived from Drosophila gene 'paired' (prd) the 'paired box' is a amino end 124 amino-acid conserved domain (signature aa 35-51: P-C-x(11)-C-V-S). Transcription factor of the helix-turn-helix structural family, DNA binding, and activating gene expression. In human, nine member proteins from Pax-1 to Pax-9. Regulate differentiation of many different tissues. Some members of the family (PAX3, PAX4, PAX6, PAX7) also contain a functional homeobox domain.
  • pedicle-
  • perichondrium-
  • perimysium-
  • phalangeal cartilage-
  • pharyngeal arches- (=branchial arches, Gk. gill) form structures of the head. Six arches form but only 4 form any structures. Each arch has a pouch, membrane and cleft.
  • pharynx- uppermost end of GIT, beginning at the buccopharyngeal membrane and at the level of the pharyngeal arches.
  • phocomelia-
  • quadratus lumborum m.-
  • quadriceps m.-
  • rectus abdominal m.-
  • sacrum-
  • scapula-
  • sclerotome- ventromedial half of each somite that forms the vertebral body and intervertebral disc.
  • segmentation- to break a solid structure into a number of usually equal size pieces.
  • serosa-
  • spinal canal- the mature space in the core of the spinal cord (filled with CSF) formed from the original lumen of the neural tube.
  • spinal cord- caudal end of neural tube that does not contribute to brain. Note: the process of secondary neuralation contributes the caudal end of the spinal cord.
  • spinal ganglia- (=dorsal root ganglia, drg) sensory ganglia derived from the neural crest lying laterally paired and dorsally to the spinal cord (in the embryo found ventral to the spinal cord). Connects centrally with the dorsal horn of the spinal cord.
  • spinal nerve- mixed nerve (motor and sensory) arising as lateral pairs at each vertebral segmental level.
  • somatic mesoderm- derived from lateral mesoderm closest to the ectoderm and separated from other component of lateral mesoderm (splanchnic, near endoderm) by the intraembryonic coelom.
  • somite- segmental block (ball) of mesoderm formed from paraxial mesoderm adjacent to notochord (axial mesoderm). Differentiates to form initially sclerotome and dermamyotome (then dermotome and myotome).
  • somitic mesoderm-
  • somitocoel- a transient cavity that appears within each of the the early forming somites then is lost.
  • somitogenesis- the process of segmentation of the paraxial mesoderm to form "mesoderm balls" beginning cranially (humans day20) and extending caudally at 1 somite/90 minutes until approx. 44 pairs have been formed.
  • sonic hedgehog- (=shh) secreted growth factor that binds patched (ptc) receptor on cell membrane. SHH function is different for different tissues in the embryo. In the nervous system, it is secreted by the notochord, ventralizes the neural tube, inducing the floor plate and motor neurons. In the Limb it is secreted by the zone of polarizing activity (ZPA) organizing limb axis formation.
  • sternum-
  • syndactyly- fusion of digits.
  • tarsal-
  • Tbx- T-box genes (transcription factor) involved in mouse forelimb (Tbx4) and hindlimb (Tbx5) specification.
  • tibia-
  • transcription factor- a factor (protein or protein with steroid) that binds to DNA to alter gene expression, usually to activate. (eg steroid hormone+receptor, Retinoic acid+Receptor, Hox, Pax, Lim, Nkx-2.2).
  • transverse abdominal m.-
  • trochanter-
  • vertebral body- formed by centrum, vertebral arch, facets for ribs. It is the mature vertebral structure formed by the 5 secondary ossification centers after puberty.
  • vertebral column- name given to the complete structure formed from the alternating segments of vertebra and intervertebral discs which support the spinal cord.
  • vertebral foramen- the dorsal cavity within each vertebra, generated by the vertebral arch that surrounds the spinal cord.
  • vertebral canal-
  • Wnt7a- The designation 'Wnt' was derived from 'wingless' and 'int'. The Wnt gene was first defined as a protooncogene, int1. Humans have at least 4 Wnt genes: Wnt7a gene is at 3p25 encoding a 349aa secreted glycoprotein. A patterning switch with different roles in different tissues. The mechanism of Wnt distribution (free diffusion, restricted diffusion and active transport) and all its possible cell receptors are still being determined. At least one WNT receptor is Frizzled (FZD). The Frizzled gene family encodes a seven-transmembrane receptor.
  • zone of polarizing activity- (zpa) dorsal region with forming limbbud mesenchyme that secretes shh and regulates limb axis formation.


Introduction | Stage 13 | Stage 22 | Musculoskeletal Stage 22 selected | Movies | Abnormalities

[skmus6.htm Somite]

[skmus7.htm Limb]

[skmus72.htm Limb Abnormalities]

[skmus8.htm Axial Skeleton][skmus8a.htm Skull]

[skmus9.htm Bone][skmus9a.htm Human Bone]

[skmus12.htm Skeletal Muscle][skmus30.htm Cartilage]

[skmus31.htm Joints][skmus50.htm Adipose]

[skmus11.htm Molecular][../MolDev/vertebra.htm Molecular - Axial]

[../Refer/skmus_ref.htm References]

[skmus_txt.htm Text only page][skmus_link.htm WWW Links]

Muscle Abnormalities

Clinical heterogeneity of duchenne muscular dystrophy (DMD): definition of sub-phenotypes and predictive criteria by long-term follow-up. Desguerre I, Christov C, Mayer M, Zeller R, Becane HM, Bastuji-Garin S, Leturcq F, Chiron C, Chelly J, Gherardi RK. PLoS One. 2009;4(2):e4347. Epub 2009 Feb 5. PMID: 19194511 | PLoS

DMD can be divided into 4 sub-phenotypes differing by severity of muscle and brain dysfunction. Simple early criteria can be used to include patients with similar outcomes in future therapeutic trials.

  1. A (early infantile DMD, 20%): severe intellectual and motor outcomes
  2. B (classical DMD, 28%): intermediate intellectual and poor motor outcome
  3. C (moderate pure motor DMD, 22%): normal intelligence and delayed motor impairment
  4. D (severe pure motor DMD, 30%)