title: Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity.
abstract: How muscle diversity is generated in the vertebrate body is poorly understood. In the limb, dorsal and ventral muscle masses constitute the first myogenic diversification, as each gives rise to distinct muscles. Myogenesis initiates after muscle precursor cells (MPCs) have migrated from the somites to the limb bud and populated the prospective muscle masses. Here, we show that Sonic hedgehog (Shh) from the zone of polarizing activity (ZPA) drives myogenesis specifically within the ventral muscle mass. Shh directly induces ventral MPCs to initiate Myf5 transcription and myogenesis through essential Gli-binding sites located in the Myf5 limb enhancer. In the absence of Shh signaling, myogenesis is delayed, MPCs fail to migrate distally, and ventral paw muscles fail to form. Thus, Shh production in the limb ZPA is essential for the spatiotemporal control of myogenesis and coordinates muscle and skeletal development by acting directly to regulate the formation of specific ventral muscles.
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Anderson
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Williams
authors.forename: Benjamin
authors.initials: B
authors.lastname: Moyon
authors.forename: Philippe
authors.initials: P
authors.lastname: Daubas
authors.forename: Shahragim
authors.initials: S
authors.lastname: Tajbakhsh
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Buckingham
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiroishi
authors.forename: Simon M
authors.initials: SM
authors.lastname: Hughes
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Borycki
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D005121:Extremities / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D018878:Limb Buds / Q000166:cytology / Q000196:embryology; D051379:Mice; D008822:Mice, Transgenic; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse