title: Autonomous and nonautonomous roles of Hedgehog signaling in regulating limb muscle formation.
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.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Jimmy Kuang-Hsien
authors.initials: JK
authors.lastname: Hu
authors.forename: Edwina
authors.initials: E
authors.lastname: McGlinn
authors.forename: Brian D
authors.initials: BD
authors.lastname: Harfe
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Kardon
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Tabin
mesh_terms: D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation; D002465:Cell Movement; D002642:Chick Embryo; D005121:Extremities / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology*; D015513:Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; C490988:Net1 protein, mouse; D015513:Oncogene Proteins