Significance
This study discloses a role for Numb in the activation and proliferation of adult muscle satellite cells and a unique function in the regulation of the muscle mass determinant Myostatin. Using two different genetic approaches to ablate
Numb
, one that ablated
Numb
in the myogenic lineage developmentally leading to reduced muscle mass. We determined that, in Numb-deficient muscle, regeneration was impaired, there was reduced stem cell proliferation, and there was an up-regulation of Myostatin. Overexpression of Numb suppressed Myostatin expression, and Myostatin-specific siRNA rescued the proliferation defect. These studies increase our knowledge of the signaling pathways involved in stem cell function and raise the possibility of regulating the Numb/Myostatin balance as a therapeutic approach to enhance muscle regeneration.