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

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35 Citations (Scopus)


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
Issue number18
Publication statusPublished - 2012

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