Vertebrate Embryo: Myogenesis and Muscle Development


The formation and patterning of three types of muscle tissues are found in vertebrates: smooth, cardiac and skeletal. All three muscle types share the property that they contract to move substances around the body (smooth and cardiac) or move and stabilise the skeleton (skeletal). Although there are common signalling pathways utilised by all muscle types, each utilises a unique pathway. The varied origins of myogenic cells and the important role of local signals coordinate the correct migration from their site of origin to final location. The local environmental signals also coordinate proliferation and expansion of myogenic precursors and finally the correct patterning, orientation and differentiation of myogenic cells. It is also evidenced that the environment continues to have an important role in the regenerative and growth of muscle tissue postnatally.

Key Concepts

  • That often the same signalling pathways are used independent of the phenotype of muscle being produced.
  • Although many different cell lineages are used to produce smooth muscle, cardiac and skeletal muscles use more specific cell lineages.
  • The environment that myogenic cells inhabit often helps to specify the early myogenic specification pathway and the later patterning of the differentiating myogenic cells into specific muscle groups and fibre types.
  • The regenerative capacity in the postnatal muscle tissue is also regulated by the environment.

Keywords: extracellular matrix; myogenesis; muscle development; stem cell niche; vertebrate muscle development

Figure 1. The hypaxial muscles delaminate from the myotome of the somite and migrate into body wall and limbs. The migratory myogenic cells are Pax3 and Pax7 positive but do not express any of the myogenic transcription factors. Within the developing limb, the myogenic cells undergo proliferation and expansion and start to now express Myf5 (Myf5+/−). As the cells become committed, they also express MyoD, it is not until the committed myogenic cells start to differentiate and fuse into myotubes that they start to express myogenin (MyoG). The satellite cells are formed early in the development of the musculature as the myogenic cells start to express Myf5. Unlike the committed myogenic cells that will differentiate, the satellite cells maintain the expression of Pax7. The satellite cells become quiescent and take up resident under the basal laminae of the muscle fibres.
Figure 2. Origins of the craniofacial myogenic cells is from the cranial paraxial mesoderm. The precursors of the extraocular muscle (red bars) are located more medially within the mesoderm. The precursors of first, second and third pharyngeal arches (blue bars) originate more laterally. The muscles of the larynx and tongue arise from the somitic mesoderm.
Figure 3. A simplified diagram of the resegmentation of the sclerotome to form the vertebra so the paraspinal muscles cross the vertebra. (a) The sclerotome will split into a smaller anterior one‐third and larger inferior two‐thirds. The sclertomal sections will reform to form the vertebra along the vertebral column, so that two sclertomal levels contribute to each vertebra. This allows the spinal nerves to exit between the vertebrae. The myotome does not split, and this results in the paraspinal muscles cross the intervertebral space and thus been able to move the vertebrae. (b) Very simplified diagram of the adult the paraspinal muscles shows how the interspinal, intertransversus and rotatores muscles that form from the myotome cross the vertebral levels.
Figure 4. The molecules involved with the specification of the regional location within the developing limb. Dorsal/ventral patterning is established by Wnt7a expression in the dorsal ectoderm of the limb (a) compared with engrailed expression in the ventral ectoderm. Within the dorsal mesenchyme of the limb, Wnt7a establishes Lmx1 expression. Members of the Hoxa and Hoxd family can be used to specify a proximal‐distal (b, Hoxa) or anterior–posterior (c, Hoxd). The superimposition of the three signalling pathways will create a specific location that will pattern the connective and myogenic cells in that region.


Abduelmula A, Huang R, Pu Q, et al. (2016) SDF‐1 controls the muscle and blood vessel formation of the somite. International Journal of Developmental Biology 60: 29–38.

Abu‐Elmagd M, Robson L, Sweetman D, et al. (2010) Wnt/Lef1 signaling acts via Pitx2 to regulate somite myogenesis. Developmental Biology 337: 211–219.

Alvares LE, Schubert FR, Thorpe C, et al. (2003) Intrinsic, Hox‐dependent cues determine the fate of skeletal muscle precursors. Developmental Cell 5: 379–390.

Ando K, Takahashi M, Yamagishi T, et al. (2011) Tenascin C may regulate the recruitment of smooth muscle cells during coronary artery development. Differentiation 81: 299–306.

Aziz A, Sebastian S and Dilworth FJ (2012) The origin and fate of muscle satellite cells. Stem Cell Reviews 8: 609–622.

Bottner M and Wedel T (2012) Abnormalities of neuromuscular anatomy in diverticular disease. Digestive Diseases 30: 19–23.

Brown CB and Baldwin HS (2006) Neural crest contribution to the cardiovascular system. Advances in Experimental Medicine and Biology 589: 134–154.

Cheng L, Alvares LE, Ahmed MU, et al. (2004) The epaxial‐hypaxial subdivision of the avian somite. Developmental Biology 274: 348–369.

Christ B and Brand‐Saberi B (2002) Limb muscle development. International Journal of Developmental Biology 46: 905–914.

Cohen ED, Ihida‐Stansbury K and Lu MM (2009) Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway. Journal of Clinical Investigation 119: 2538–2549.

Daughters RS, Keirstead SA and Slack JM (2016) Transformation of jaw muscle satellite cells to cardiomyocytes. Differentiation 93: 58–65.

Desjardins CA and Naya FJ (2016) The function of the MEF2 family of transcription factors in cardiac development, cardiogenomics, and direct reprogramming. Journal of Cardiovascular Development and Disease 3: 26.

Du SJ, Tan X and Zhang J (2014) SMYD proteins: key regulators in skeletal and cardiac muscle development and function. Anatomical Record (Hoboken) 297: 1650–1662.

Duprez D, Lapointe F, Edom‐Vovard F, et al. (1999) Sonic hedgehog (SHH) specifies muscle pattern at tissue and cellular chick level, in the chick limb bud. Mechanisms of Development 82: 151–163.

Firulli AB, Miano JM, Bi W, et al. (1996) Myocyte enhancer binding factor‐2 expression and activity in vascular smooth muscle cells. Association with the activated phenotype. Circulation Research 78: 196–204.

Francis‐West PH, Robson L and Evans DJR (2003) Craniofacial development: the tissue and molecular interactions that control development of the head. Advances in Anatomy Embryology and Cell Biology 169: 79–81.

Fredette BJ and Landmesser LT (1991) Relationship of primary and secondary myogenesis to fiber type development in embryonic chick muscle. Developmental Biology 143: 1–18.

Gabella G (2002) Development of visceral smooth muscle. Results and Problems in Cell Differentiation 38: 1–37.

Goss AM, Tian Y and Cheng L (2011) Wnt2 signaling is necessary and sufficient to activate the airway smooth muscle program in the lung by regulating myocardin/Mrtf‐B and Fgf10 expression. Developmental Biology 356: 541–552.

Grifone R, Jarry T, Dandonneau M, et al. (2008) Properties of branchiomeric and somite‐derived muscle development in Tbx1 mutant embryos. Developmental Dynamics 237: 3071–3078.

Harel I, Nathan E and Tirosh‐Finkel L (2009) Distinct origins and genetic programs of head muscle satellite cells. Developmental Cell 16: 822–832.

Ihida‐Stansbury K, Ames J, Chokshi M, et al. (2015) Role played by Prx1‐dependent extracellular matrix properties in vascular smooth muscle development in embryonic lungs. Pulmonary Circulation 5: 382–397.

Iida K, Hidaka K, Takeuchi M, et al. (1999) Expression of MEF2 genes during human cardiac development. Tohoku Journal of Experimental Medicine 187: 15–23.

Jayewickreme CD and Shivdasani RA (2015) Control of stomach smooth muscle development and intestinal rotation by transcription factor BARX1. Developmental Biology 405: 21–32.

Kengaku M, Capdevila J, Rodriguez‐Esteban C, et al. (1998) Distinct WNT pathways regulating AER formation and dorsoventral polarity in the chick limb bud. Science 280: 1274–1277.

Ladd AN, Yatskievych TA and Antin PB (1998) Regulation of avian cardiac myogenesis by activin/TGFbeta and bone morphogenetic proteins. Developmental Biology 204: 407–419.

Lee AS, Harris J, Bate M, et al. (2013) Initiation of primary myogenesis in amniote limb muscles. Developmental Dynamics 242: 1043–1155.

Logan C, Hornbruch A, Campbell I and Lumsden A (1997) The role of Engrailed in establishing the dorsoventral axis of the chick limb. Development 124: 2317–2324.

Majesky MW (2007) Developmental basis of vascular smooth muscle diversity. Arteriosclerosis, Thrombosis, and Vascular Biology 27: 1248–1258.

Matsakas A, Otto A and Elashry MI (2010) Altered primary and secondary myogenesis in the myostatin‐null mouse. Rejuvenation Research 13: 717–727.

Musumeci G, Castrogiovanni P, Coleman R, et al. (2015) Somitogenesis: from somite to skeletal muscle. Acta Histochemica 117: 313–328.

Nakamura T, Sano M, Songyang Z and Schneider MD (2003) A Wnt‐ and beta‐catenin‐dependent pathway for mammalian cardiac myogenesis. Proceedings of the National Academy of Sciences of the United States of America 100: 5834–5839.

Ono Y, Boldrin L, Knopp P, et al. (2010) Muscle satellite cells are a functionally heterogeneous population in both somite‐derived and branchiomeric muscles. Developmental Biology 337: 29–41.

Otto A, Macharia R and Matsakas A (2010) A hypoplastic model of skeletal muscle development displaying reduced foetal myoblast cell numbers, increased oxidative myofibres and improved specific tension capacity. Developmental Biology 343: 51–62.

Owens GK, Kumar MS and Wamhoff BR (2004) Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiological Reviews 84: 767–801.

Parada C, Han D and Chai Y (2012) Molecular and cellular regulatory mechanisms of tongue myogenesis. Journal of Dental Research 91: 528–535.

de Pater E, Ciampricotti M, Priller F, et al. (2012) Bmp signaling exerts opposite effects on cardiac differentiation. Circulation Research 110: 578–587.

Pownall ME, Gustafsson MK and Emerson CP (2002) Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos. Annual Review of Cell and Developmental Biology 18: 747–783.

Prunotto C, Crepaldi T and Forni PE (2004) Analysis of Mlc‐lacZ Met mutants highlights the essential function of Met for migratory precursors of hypaxial muscles and reveals a role for Met in the development of hyoid arch‐derived facial muscles. Developmental Dynamics 231: 582–591.

Sato Y (2013) Dorsal aorta formation: separate origins, lateral‐to‐medial migration, and remodelling. Development, Growth and Differentiation 55: 113–129.

von Scheven G, Bothe I, Ahmed MU, et al. (2006) Protein and genomic organisation of vertebrate MyoR and Capsulin genes and their expression during avian development. Gene Expression Patterns 6: 383–393.

Snijders T, Nederveen JP, McKay BR, et al. (2015) Satellite cells in human skeletal muscle plasticity. Frontiers in Physiology 6: 283.

Tozer S, Bonnin MA and Relaix F (2007) Involvement of vessels and PDGFB in muscle splitting during chick limb development. Development 134: 2579–2591.

Tzahor E (2015) Head muscle development. Results and Problems in Cell Differentiation 56: 123–142.

Untergasser G, Gander R, Lilg C, et al. (2005) Profiling molecular targets of TGF‐beta1 in prostate fibroblast‐to‐myofibroblast transdifferentiation. Mechanisms of Ageing and Development 126: 59–69.

Valasek P, Theis S, DeLaurier A, et al. (2011) Cellular and molecular investigations into the development of the pectoral girdle. Developmental Biology 357: 108–116.

Wasteson P, Johansson BR, Jukkola T, et al. (2008) Developmental origin of smooth muscle cells in the descending aorta in mice. Development 135: 1823–1832.

Webb SE, Lee KK, Tang MK and Ede DA (1997) Fibroblast growth factors 2 and 4 stimulate migration of mouse embryonic limb myogenic cells. Developmental Dynamics 209: 206–216.

Xin M, Davis CA, Molkentin JD, et al. (2006) A threshold of GATA4 and GATA6 expression is required for cardiovascular development. Proceedings of the National Academy of Sciences of the United States of America 103: 11189–11194.

Yamamoto M, Gotoh Y, Tamura K, et al. (1998) Coordinated expression of Hoxa‐11 and Hoxa‐13 during limb muscle patterning. Development 125: 1325–1335.

Yan J, Zhang L, Xu J, et al. (2014) Smad4 regulates ureteral smooth muscle cell differentiation during mouse embryogenesis. PLoS One 9: e104503.

Yang Y, Relan NK, Przywara DA and Schuger L (1999) Embryonic mesenchymal cells share the potential for smooth muscle differentiation: myogenesis is controlled by the cell's shape. Development 126: 3027–3033.

Yin H, Price F and Rudnicki MA (2013) Satellite cells and the muscle stem cell niche. Physiological Reviews 93: 23–67.

Yusuf F and Brand‐Saberi B (2012) Myogenesis and muscle regeneration. Histochemistry and Cell Biology 138: 187–199.

Further Reading

Bryson‐Richardson RJ and Currie PD (2008) The genetics of vertebrate myogenesis. Nature Reviews Genetics 9: 632–646.

Buckingham M (2006) Myogenic progenitor cells and skeletal myogenesis in vertebrates. Current Opinion in Genetics and Development 16: 525–532.

DeLaurier A, Schweitzer R and Logan M (2006) Pitx1 determines the morphology of muscle, tendon, and bones of the hindlimb. Developmental Biology 299: 22–34.

Eisenberg LM and Markwald RR (2004) Cellular recruitment and the development of the myocardium. Developmental Biology 274: 225–232.

Evans DJ, Valasek P, Schmidt C, et al. (2006) Skeletal muscle translocation in vertebrates. Anatomy and Embryology (Berlin) 211 (suppl 1): 43–50.

Lv F, Zhu C, Yan X, Wang X and Liu D (2016) Generation of a Mef2aa: EGFP transgenic zebrafish line that expresses EGFP in muscle cells. Fish Physiology and Biochemsitry 43: 287–294.

Maroto M, Iimura T, Dale JK, et al. (2008) BHLH proteins and their role in somitogenesis. Adv. Exp. Med. Biol. 638: 124–139.

McLoon LK, Thorstenson KM, Solomon A and Lewis MP (2007) Myogenic precursor cells in craniofacial muscles. Oral Diseases 13: 134–140.

Vivarelli E, Brown WE, Whalen RG and Cossu G (1988) The expression of slow myosin during mammalian somitogenesis and limb bud differentiation. Journal of Cell Biology 107: 2191–2197.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Robson, Lesley G(Oct 2017) Vertebrate Embryo: Myogenesis and Muscle Development. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0026598]