Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity

Claire Anderson, Victoria C. Williams, Benjamin Moyon, Philippe Daubas, Shahragim Tajbakhsh, Margaret E. Buckingham, Toshihiko Shiroishi, Simon Hughes, Anne-Gaelle Borycki*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2103-2117
Number of pages15
JournalGenes and Development
Volume26
Issue number18
DOIs
Publication statusPublished - 15 Sept 2012

Keywords

  • myogenesis
  • MOUSE EMBRYOGENESIS
  • VERTEBRATE LIMB
  • TRANSCRIPTION FACTORS
  • Shh
  • Myf5
  • PROGENITOR CELLS
  • CHICK LIMB
  • limb
  • SKELETAL-MUSCLE
  • TRANSGENIC MICE
  • MYOGENIC CELLS
  • MYF5 EXPRESSION
  • MYOD TRANSCRIPTION

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