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Stem Cell Reports. 2014 Sep 9;3(3):475-88. doi: 10.1016/j.stemcr.2014.06.019. Epub 2014 Jul 31.

Transiently active Wnt/β-catenin signaling is not required but must be silenced for stem cell function during muscle regeneration.

Author information

1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
2
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: gkardon@genetics.utah.edu.

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.

PMID:
25241745
PMCID:
PMC4266007
DOI:
10.1016/j.stemcr.2014.06.019
[Indexed for MEDLINE]
Free PMC Article

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