Autonomous and nonautonomous roles of hedgehog signaling in regulating limb muscle formation

Jimmy K-H Hu, Edwina McGlinn, Brian D Harfe, Gabrielle Kardon, Clifford J Tabin

Research output: Contribution to journalArticleResearchpeer-review

35 Citations (Scopus)

Abstract

Muscle progenitor cells migrate from the lateral somites into the developing vertebrate limb, where they undergo patterning and differentiation in response to local signals. Sonic hedgehog (Shh) is a secreted molecule made in the posterior limb bud that affects patterning and development of multiple tissues, including skeletal muscles. However, the cell-autonomous and non-cell-autonomous functions of Shh during limb muscle formation have remained unclear. We found that Shh affects the pattern of limb musculature non-cell-autonomously, acting through adjacent nonmuscle mesenchyme. However, Shh plays a cell-autonomous role in maintaining cell survival in the dermomyotome and initiating early activation of the myogenic program in the ventral limb. At later stages, Shh promotes slow muscle differentiation cell-autonomously. In addition, Shh signaling is required cell-autonomously to regulate directional muscle cell migration in the distal limb. We identify neuroepithelial cell transforming gene 1 (Net1) as a downstream target and effector of Shh signaling in that context.
Original languageEnglish
Pages (from-to)2088 - 2102
Number of pages15
JournalGenes & Development
Volume26
Issue number18
DOIs
Publication statusPublished - 2012

Cite this