During postnatal growth, satellite cells (skeletal muscle stem cells) divide to provide new myonuclei for growing muscle fibres, but in adult muscle they are maintained in an undifferentiated quiescent state except during muscle regeneration. Notch signalling regulates stem cells in many tissues, including skeletal muscle, and here, So-ichiro Fukada and co-workers investigate whether the Notch target genes Hesr1 and Hesr3 are involved in the generation of satellite cells (). They report that Hesr1 and Hesr3 are expressed simultaneously in neonatal and adult mouse satellite cells and show that, although Hesr1 and Hesr3 single-knockout mice have no obvious satellite cell or muscle regeneration abnormalities, the postnatal generation of undifferentiated quiescent satellite cells is impaired in Hesr1/3 double-knockout mice. Moreover, satellite cell numbers gradually decrease in Hesr1/3 double-knockout mice because of premature differentiation, and the mice develop an age-dependent muscle regeneration defect. Thus, the researchers conclude, Hesr1 and Hesr3 play crucial roles in skeletal muscle homeostasis by regulating the undifferentiated quiescent state of satellite cells.
