Musculoskeletal System - Muscle Development

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Endochondral bone


There are 3 different types of muscle: skeletal, cardiac and smooth. This page describes skeletal muscle development, descriptions of cardiac muscle and smooth muscle development can be found in other notes. Skeletal muscle forms by fusion of mononucleated myoblasts to form mutinucleated myotubes.

Differentiation/determination of mesoderm into muscle cells is thought to involve a family of basic Helix-Loop-Helix transcription factors, the first of which discovered was MyoD1. MyoD1 needs to form a dimer to be active and is maintained in an inactive state by binding of an inhibitor, Id.

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

  • Notch regulation of myogenic versus endothelial fates of cells that migrate from the somite to the limb[1] "Multipotent Pax3-positive (Pax3(+)) cells in the somites give rise to skeletal muscle and to cells of the vasculature. We had previously proposed that this cell-fate choice depends on the equilibrium between Pax3 and Foxc2 expression. In this study, we report that the Notch pathway promotes vascular versus skeletal muscle cell fates. ...We now demonstrate that in addition to the inhibitory role of Notch signaling on skeletal muscle cell differentiation, the Notch pathway affects the Pax3:Foxc2 balance and promotes the endothelial versus myogenic cell fate, before migration to the limb, in multipotent Pax3(+) cells in the somite of the mouse embryo." Limb Development
  • Jamb and jamc are essential for vertebrate myocyte fusion[2] "Cellular fusion is required in the development of several tissues, including skeletal muscle. In vertebrates, this process is poorly understood and lacks an in vivo-validated cell surface heterophilic receptor pair that is necessary for fusion. Identification of essential cell surface interactions between fusing cells is an important step in elucidating the molecular mechanism of cellular fusion. We show here that the zebrafish orthologues of JAM-B and JAM-C receptors are essential for fusion of myocyte precursors to form syncytial muscle fibres. Both jamb and jamc are dynamically co-expressed in developing muscles and encode receptors that physically interact." (mammalian orthologues JAM-B/Jam2a = JAM2 JAM-C/Jam3b = JAM3)
  • Origin of vertebrate limb muscle: the role of progenitor and myoblast populations[3] (review) "Muscle development, growth, and regeneration take place throughout vertebrate life. In amniotes, myogenesis takes place in four successive, temporally distinct, although overlapping phases. Understanding how embryonic, fetal, neonatal, and adult muscle are formed from muscle progenitors and committed myoblasts is an area of active research. In this review we examine recent expression, genetic loss-of-function, and genetic lineage studies that have been conducted in the mouse, with a particular focus on limb myogenesis."
  • The histone methyltransferase Set7/9 promotes myoblast differentiation and myofibril assembly [4] Together, our experiments define a biological function for Set7 in muscle differentiation and provide a molecular mechanism by which Set7 modulates myogenic transcription factors during muscle differentiation.
  • The expression pattern of myogenic regulatory factors MyoD, Myf6 and Pax7 in postnatal porcine skeletal muscles[5] "The MyoD, Myf6 genes, which belong to the family of muscle regulatory factors (MRFs) play a major role in muscle growth and development. These basic helix-loop-helix (bHLH) transcription factors regulate myogenesis: they initiate the formation of muscle fibres and regulate the transcription of muscle specific genes. The paired-box transcription factor Pax7 plays critical roles during fetal development and this protein is essential for renewal and maintenance of muscle stem cells. In particular, expression of Pax7 and MyoD is correlated with presence of active satellite cells, important in hyperplastic and hypertrophic growth in skeletal muscle."
  • Expression of Gα(z) in C2C12 cells restrains myogenic differentiation [6] "The recent identification of Gα(z) expression in C2C12 myoblasts and its demonstrated interaction with the transcription factor Eya2 inferred an unanticipated role of Gα(z) in muscle development. In the present study, endogenous Gα(z) mRNA and protein expressions in C2C12 cells increased upon commencement of myogenesis and peaked at around 4-6days after induction but were undetectable in adult skeletal muscle. "
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Somites in human embryo (Carnegie stage 11)

Three different types of muscle form in the body.

  • Skeletal muscle - cells originate from the paraxial mesoderm, forming somites, then dermamyotome and finally the myotome. Myoblasts undergo frequent divisions and coalesce with the formation of a multinucleated, syncytial muscle fibre or myotube. The nuclei of the myotube are still located centrally in the muscle fibre. In the course of the synthesis of the myofilaments/myofibrils, the nuclei are gradually displaced to the periphery of the cell.
  • Cardiac muscle - cells originate from the prechordal splanchnic mesoderm.
  • Smooth muscle - cells originate from undifferentiated mesenchymal cells. These cells differentiate first into mitotically active cells, myoblasts, which contain a few myofilaments. Myoblasts give rise to the cells which will differentiate into mature smooth muscle cells.

Somite cartoon3.pngSomite cartoon4.pngSomite cartoon5.png

Muscle Groups

Cartoon showing myotome fate forming epaxial and hypaxial muscle groups.

Epaxial Muscle

Anatomical term describing skeletal muscles which lie dorsal (posterior) to the vertebral column developing from the somite myotome. In humans, this is only a small muscle group formed by the transversospinalis, longissimus, and iliocostalis muscles. Also at the ribcage level the levatores costarum muscles involved with rib elevation during respiration. The body muscles lying ventral (anterior) to the vertebral column are the hypaxial muscles.

Hypaxial Muscle

(hypomere) Anatomical term describing skeletal muscles which lie ventral (anterior) to the vertebral column developing from the somite myotome. These muscles contribute both body (trunk) and limb skeletal muscle.

  • In the trunk, these form the three anterior body muscle layers.
  • In the limb, these form the extensor and flexor muscle groups.

Head Muscle

  • jaw associated muscles mainly from cranial mesoderm.
  • jaw, connective tissues and tendons from neural crest cells.

Head muscle precursor myoblast summary from a review.[7]

  • myoblasts for the tongue muscle, migrate like those seen in the limb.
  • myoblasts for extraocular muscles, condense within paraxial mesoderm, then cross the mesoderm:neural crest interface en route to periocular regions.
  • myoblasts for branchial muscle, establish contacts with neural crest populations before branchial arch formation and maintain these relations through subsequent stages of development.

See also for head muscle and connective tissue.[8]

Skeletal Muscle Stages

3D virtual muscle model[9]
3D virtual muscle model[9]

Myoblast - individual progenitor cells

Myotube - multinucleated, but undifferentiated contractile apparatus (sarcomere)

Myofibre (myofiber, muscle cell) - multinucleated and differentiated sarcomeres

  • primary myofibres - first-formed myofibres, act as a structural framework upon which myoblasts proliferate, fuse in linear sequence
  • secondary myofibers - second later population of myofibres that form surrounding the primary fibres.

Muscle Fibre Types

Muscle fiber types

Muscle fiber types

  • type IIB, IIA, IIX, and I fibres - based only on the myosin ATPase activity.
    • Type I fibres appear red, due to the presence of myoglobin.
    • Type II fibres appear white, due to the absence of myoglobin and their glycolytic nature.
  • A group of individual myofibres within a muscle will be innervated by a single motor neuron (motor unit).
  • The electrical properties of the motor neuron will regulate the contractile properties of all associated myofibres.
Fibre Type Type I fibres Type II a fibres Type II x fibres Type II b fibres
Contraction time Slow Moderately Fast Fast Very fast
Size of motor neuron Small Medium Large Very large
Resistance to fatigue High Fairly high Intermediate Low
Activity Used for Aerobic Long-term anaerobic Short-term anaerobic Short-term anaerobic
Maximum duration of use Hours <30 minutes <5 minutes <1 minute
Power produced Low Medium High Very high
Mitochondrial density High High Medium Low
Capillary density High Intermediate Low Low
Oxidative capacity High High Intermediate Low
Glycolytic capacity Low High High High
Major storage fuel Triglycerides Creatine phosphate, glycogen Creatine phosphate, glycogen Creatine phosphate, glycogen
Myosin heavy chain,
human genes

Muscle Contraction

Skeletal muscle sarcomeres

Individual myoblasts in the developing muscle bed initial fuse together to form multi-nucleated myotubes. These myotubes then express the contractile proteins, that are organized into sarcomeres in series along the length of the myotube.

This animation shows the molecular interactions that occur within the skeletal muscle sarcomere between actin and myosin during skeletal muscle contraction.


  • Moving blob and stick - myosin complex.
  • Moving blob and stick - myosin complex with ATPase activation.
  • Ball binding myosin and splitting - ATP losing a phosphate to form ADP.
  • Twisted string of beads - actin helix.
  • Blue string - tropomyosin.
  • Beads stacked on large bead on blue string - troponin.
  • Small ball binding troponin - Calcium ion (Ca2+).
  • Grey pyramid - Magnesiun ion (Mg2+).
Actin myosin crossbridge 3D animation.gif


In both development and the adult, the group of skeletal muscles supplied by a specific segmental spinal nerve is referred to as a myotome. The muscle arises from a specific somite and the spinal nerve arises from a specific level of the spinal cord (identified by veretebral column).

In humans this corresponds to the following spinal nerves (from top to bottom) and muscular functions:

  • C3,4 and 5 supply the diaphragm for breathing.
  • C5 supply shoulder muscles and muscles to bend our elbow.
  • C6 for bending the wrist back.
  • C7 for straightening the elbow.
  • C8 bends the fingers.
  • T1 spreads the fingers.
  • T1 –T12 supplies the chest wall and abdominal muscles.
  • L2 bends the hip.
  • L3 straightens the knee.
  • L4 pulls the foot up.
  • L5 wiggles the toes.
  • S1 pulls the foot down.
  • S3,4 and 5 supply the bladder, bowel, sex organs, anal and other pelvic muscles.

Mouse Limb Muscle

Mouse limb tissue development.jpg

Change in cell types and tissue formation as a function of mouse developmental stage.[10]

Links: Mouse Development

Histology Images

Muscle Histology: Muscle Development | Human HE x4 longitudinal and transverse | Human HE x40 transverse | Human HE x40 longitudinal | Human HE x40 longitudinal | Human HE x4 longitudinal and transverse | Muscle Spindle HE x40 | Human HE x40 | Human HE x40 | Human HE x40 | Human HE x100 | Human HE x100 | Fetal human muscle | Myotendinous junction label | Myotendinous junction HE x40 | Whipf 1 | Whipf 2 | Whipf 3 | Tongue HE x10 transverse | Tongue x100 | Muscle spindle HE x20 | Muscle spindle HE x40

Electron Microscopy Virtual Slides

Electron micrographs below are thin longitudinal section cut through adult human skeletal muscle tissue.

Skeletal Muscle EM1


 ‎‎Mobile | Desktop | Original

Skeletal Muscle | EM Slides
Skeletal Muscle EM2


 ‎‎Mobile | Desktop | Original

Skeletal Muscle | EM Slides
Skeletal Muscle EM3


 ‎‎Mobile | Desktop | Original

Skeletal Muscle | EM Slides
Skeletal Muscle EM4


 ‎‎Mobile | Desktop | Original

Skeletal Muscle | EM Slides
Skeletal Muscle EM5


 ‎‎Mobile | Desktop | Original

Skeletal Muscle | EM Slides

Image Source: Contributed by Dartmouth College Electron Microscope Facility special thanks to Chuck Daghlian and Louisa Howard. Gallery. Original images may have been altered in size contrast and labelling. (These images are in the public domain)

Links: Electron Microscopy Virtual Slides


  • Musculoskeletal mass doubles by the end of puberty
  • regulated growth by - sex steroid hormones, growth hormone, insulin-like growth factors
  • accumulation of (peak) bone mass during puberty relates to future osteoporosis in old age


There can be abnormalities associated directly with muscle differentiation and function as well as those mediated indirectly by abnormalities of innervation or skeletal development and other associated systems.

Duchenne Muscular Dystrophy

The most common occuring in Boys and in Duchenne Muscular Dystrophy (DMD). This cause of the disease was discovered in 1988 as a mutation in dystrophin, a protein that lies under the muscle fiber membrane and maintains the cell's integrity. As skeletal muscles have little prenatal load or use it is not until postnatally that muscle wasting occurs, usually in the anti-gravity muscles first. This is a progressive disease usually detected between 3-5 years old.

  • X-linked dystrophy
  • large gene encoding cytoskeletal protein - Dystrophin
  • progressive wasting of muscle, die late teens

Becker Muscular Dystrophy

A milder adult (30-40 years old) onset form of the disease Becker's Muscular Dystrophy (BMD) that involves mutations in the same dystrophin gene.

Autosomal Recessive Muscular Dystrophy

Dystroglycan, a protein that associates with both dystrophin and membrane molecules, is a candidate gene for the site of the mutation in autosomal recessive muscular dystrophies. A knockout mouse has been generated that has early developmental abnormalities.

Myotonic Dystrophy

An inherited disorder in which the muscles contract but have decreasing power to relax. With this condition, the muscles also become weak and waste away. The myotonic dystrophy gene, found on chromosome 19, codes for a protein kinase that is found in skeletal muscle, where it likely plays a regulatory role. The disease is "amplified" through generations probably by a similar GC expansion associated with Huntington disease.

Facioscapulohumeral muscular dystrophy (FSHD)

  • characterized by the progressive weakness and atrophy of a specific subset of skeletal muscles.
  • mostly affects the muscles of the face, scapula, and upper arms.
    • involvement of specific muscles that it is often used clinically to distinguish FSHD from other forms of muscular dystrophy.

Links: Musculoskeletal Abnormalities | PLoS Currents - Muscular Dystrophy


  1. <pubmed>24927569</pubmed>
  2. <pubmed>22180726</pubmed>
  3. <pubmed>21621065</pubmed>
  4. <pubmed>21859860</pubmed>
  5. <pubmed>20888930</pubmed>
  6. <pubmed>20946953</pubmed>
  7. <pubmed>16502415</pubmed>
  8. <pubmed>19198652</pubmed>
  9. 9.0 9.1 <pubmed>18945372</pubmed>| PMC2596796 | BMC Syst Biol.
  10. <pubmed>22174793</pubmed>


<pubmed>22274696</pubmed> <pubmed>21621065</pubmed> <pubmed>21183656</pubmed> <pubmed>20553711</pubmed> <pubmed>19762225</pubmed> <pubmed>16118057</pubmed>


<pubmed>21859860</pubmed> <pubmed>20195544</pubmed> <pubmed>20037161</pubmed> <pubmed>19198652</pubmed>

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June 2010 " Skeletal Muscle Development" All (19316) Review (2515) Free Full Text (5587)

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Cite this page: Hill, M.A. (2020, October 21) Embryology Musculoskeletal System - Muscle Development. Retrieved from

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