Abstract
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.
Highlights
Vertebrate skeletal muscle arises during embryonic, fetal, and adult stages
The tyrosine phosphatase Ptpn11 is an important transducer of signals provided by growth factors and cytokines (Grossmann et al, 2010; Neel et al, 2003)
We demonstrate here that Ptpn11 plays a central role in myogenesis
Summary
Vertebrate skeletal muscle arises during embryonic, fetal, and adult stages. The Pax7+ cells give rise to primary fibers in embryos, permit growth of muscle mass during fetal and postnatal muscle development as well as repair of injured muscle in the adult (Sambasivan et al, 2011; Lepper et al, 2011; McCarthy et al, 2011; Murphy et al, 2011). Fetal and postnatal Pax7+ cells proliferate, but most reach quiescence when muscle fibers cease to grow by accretion of nuclei (around P21 in mice; White et al, 2010). Even in the muscle of adult sedentary mice, a small proportion of satellite cells remains in the cell cycle
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