title: Transiently active Wnt/β-catenin signaling is not required but must be silenced for stem cell function during muscle regeneration.
abstract: Adult muscle's exceptional capacity for regeneration is mediated by muscle stem cells, termed satellite cells. As with many stem cells, Wnt/β-catenin signaling has been proposed to be critical in satellite cells during regeneration. Using new genetic reagents, we explicitly test in vivo whether Wnt/β-catenin signaling is necessary and sufficient within satellite cells and their derivatives for regeneration. We find that signaling is transiently active in transit-amplifying myoblasts, but is not required for regeneration or satellite cell self-renewal. Instead, downregulation of transiently activated β-catenin is important to limit the regenerative response, as continuous regeneration is deleterious. Wnt/β-catenin activation in adult satellite cells may simply be a vestige of their developmental lineage, in which β-catenin signaling is critical for fetal myogenesis. In the adult, surprisingly, we show that it is not activation but rather silencing of Wnt/β-catenin signaling that is important for muscle regeneration.
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Malea M
authors.initials: MM
authors.lastname: Murphy
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Keefe
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Lawson
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Flygare
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Yandell
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: gkardon@genetics.utah.edu.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Kardon
mesh_terms: D000818:Animals; D002460:Cell Line; D020868:Gene Silencing; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development; D009132:Muscles / Q000293:injuries / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics*
chemical_list: D051176:beta Catenin