During early development, skeletal muscle stem/progenitor cells (SMSPCs) are thought to reside in low O2 levels but how this hypoxic environment affects myogenesis in vivo is unclear. Here, Celeste Simon and colleagues investigate the role of hypoxia inducible factor 1α (HIF1α), which mediates the cellular sensing of O2, during skeletal muscle development and regeneration in mice (p. ). They first show that HIF1α is in fact dispensable for embryonic and fetal myogenesis; the inactivation of Hif1a in PAX3-expressing SMSPCs does not affect progenitor cell homeostasis or the formation of embryonic and fetal muscles. In contrast, they report, the deletion of Hif1a in PAX7-expressing progenitors in adult mice accelerates muscle regeneration after ischemic injury, suggesting that HIF1α normally acts to impede muscle regeneration. The researchers further demonstrate that HIF1α represses the canonical Wnt signalling pathway, which is known to promote muscle regeneration after injury. Together, these findings confirm that the HIF pathway regulates myogenesis in vivo and reveal a novel link between O2 sensing and Wnt signalling during development and regeneration.
