The equilibrium between proliferation and quiescence of myogenic progenitor
and stem cells is tightly regulated to ensure appropriate skeletal muscle
growth and repair. The non-receptor tyrosine phosphatase Ptpn11 (Shp2) is an
important transducer of growth factor and cytokine signals. Here we combined
complex genetic analyses, biochemical studies and pharmacological interference
to demonstrate a central role of Ptpn11 in postnatal myogenesis of mice. Loss
of Ptpn11 drove muscle stem cells out of the proliferative and into a resting
state during muscle growth. This Ptpn11 function was observed in postnatal but
not fetal myogenic stem cells. Furthermore, muscle repair was severely
perturbed when Ptpn11 was ablated in stem cells due to a deficit in stem cell
proliferation and survival. Our data demonstrate a molecular difference in the
control of cell cycle withdrawal in fetal and postnatal myogenic stem cells,
and assign to Ptpn11 signaling a key function in satellite cell activity