Abstract

Skeletal muscle in vertebrates is formed by two major routes, as illustrated by the mouse embryo. Somites give rise to myogenic progenitors that form all of the muscles of the trunk and limbs. The behavior of these cells and their entry into the myogenic program is controlled by gene regulatory networks, where paired box gene 3 (Pax3) plays a predominant role. Head and some neck muscles do not derive from somites, but mainly form from mesoderm in the pharyngeal region. Entry into the myogenic program also depends on the myogenic determination factor (MyoD) family of genes, but Pax3 is not expressed in these myogenic progenitors, where different gene regulatory networks function, with T-box factor 1 (Tbx1) and paired-like homeodomain factor 2 (Pitx2) as key upstream genes. The regulatory genes that underlie the formation of these muscles are also important players in cardiogenesis, expressed in the second heart field, which is a major source of myocardium and of the pharyngeal arch mesoderm that gives rise to skeletal muscles. The demonstration that both types of striated muscle derive from common progenitors comes from clonal analyses that have established a lineage tree for parts of the myocardium and different head and neck muscles. Evolutionary conservation of the two routes to skeletal muscle in vertebrates extends to chordates, to trunk muscles in the cephlochordate Amphioxus and to muscles derived from cardiopharyngeal mesoderm in the urochordate Ciona, where a related gene regulatory network determines cardiac or skeletal muscle cell fates. In conclusion, Eric Davidson’s visionary contribution to our understanding of gene regulatory networks and their evolution is acknowledged.

Highlights

  • Skeletal muscle in vertebrates is formed by two major routes, as illustrated by the mouse embryo

  • The chemokine receptor type 4 (CXCR4) is required for migration of a subset of myogenic progenitors into the limb. Activation of this gene depends on a transcription factor encoded by ladybird homeobox 1 (Lbx1), which lies genetically downstream of paired box gene 3 (Pax3)

  • Dye-I labeling of cells in cultured mouse embryos shows that some cells from the posterior part of the second heart field (SHF), which is the source of myocardial cells at the venous pole of the heart, migrate anteriorly, acquire gene expression patterns typical of the anterior SHF, and contribute to outflow tract myocardium that will form the base of the pulmonary trunk [35]

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Summary

Skeletal Muscles of the Trunk and Limbs

All of the skeletal muscles present in the trunk and limbs are derived from somites, segments of paraxial mesoderm that form progressively on either side of the body axis from the anterior to the posterior of the developing embryo [1]. In the initial waves of epaxial and hypaxial myogenesis, myogenic progenitors enter the muscle program and differentiate into muscle It is only later, when the epithelial structure of the central dermomyotome breaks down and cells enter the underlying muscle masses, that some of these cells do not differentiate, but constitute a reserve of myogenic progenitors for subsequent muscle growth and later muscle regeneration. The gene regulatory network [2] that governs muscle progenitor cell behavior (Fig. 1A) and controls activation of the myogenic determination genes (Fig. 1B) is dominated by paired box factor 3 gene (Pax3) [3], which is first expressed in presomitic mesoderm immediately anterior to the first somite and throughout the early epithelial somite, before becoming restricted to myogenic progenitors of the dermomyotome.

COLLOQUIUM PAPER
Skeletal Muscles of the Head and Neck
Extraocular muscles
Cardiac Muscle and the Second Heart Field
Cell Lineage Analyses
Right Superior Caval Vein
Evolutionary Considerations
Concluding Remarks
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