The transition from differentiation to growth during dermomyotome-derived myogenesis depends on temporally restricted hedgehog signaling Journal Article


Author(s): Kahane, Nitza; Ribes, Vanessa; Kicheva, Anna; Briscoe, James; Kalcheim, Chaya
Article Title: The transition from differentiation to growth during dermomyotome-derived myogenesis depends on temporally restricted hedgehog signaling
Affiliation
Abstract: The development of a functional tissue requires coordination of the amplification of progenitors and their differentiation into specific cell types. The molecular basis for this coordination during myotome ontogeny is not well understood. Dermomytome progenitors that colonize the myotome first acquire myocyte identity and subsequently proliferate as Pax7-expressing progenitors before undergoing terminal differentiation. We show that the dynamics of sonic hedgehog (Shh) signaling is crucial for this transition in both avian and mouse embryos. Initially, Shh ligand emanating from notochord/floor plate reaches the dermomyotome, where it both maintains the proliferation of dermomyotome cells and promotes myogenic differentiation of progenitors that colonized the myotome. Interfering with Shh signaling at this stage produces small myotomes and accumulation of Pax7-expressing progenitors. An in vivo reporter of Shh activity combined with mouse genetics revealed the existence of both activator and repressor Shh activities operating on distinct subsets of cells during the epaxial myotomal maturation. In contrast to observations in mice, in avians Shh promotes the differentiation of both epaxial and hypaxial myotome domains. Subsequently, myogenic progenitors become refractory to Shh; this is likely to occur at the level of, or upstream of, smoothened signaling. The end of responsiveness to Shh coincides with, and is thus likely to enable, the transition into the growth phase of the myotome.
Keywords: Avian embryo; Gli; Myf5; Myotome; Somite
Journal Title: Development
Volume: 140
Issue 8
ISSN: 1477-9129
Publisher: Company of Biologists  
Date Published: 2013-04-18
Start Page: 1740
End Page: 1750
DOI: 10.1242/dev.092726
Notes: This study was supported by grants from the Israel Science Foundation (ISF) [11/09 to C.K.]; the Association Francaise contre les Myopathies (AFM) [15642 to C.K.]; the German Research Foundation (DFG) [UN 34/27-1 to C.K.]; the UK Medical Research Council (MRC) [U117560541 to J.B. and A.K.]; Fondation Pour la Recherche M├ędicale (FRM) (post-doctoral fellowship to V.R.). Deposited in PMC for release after 6 months
Open access: no