Transcription factors providing myogenic identity to adult muscle satellite cells

Abstract

Satellite cells are an adult stem cell population that provide for the regeneration of skeletal muscle. Two major families of transcription factors, the paired-box (Pax) factors and the myogenic regulatory factors (MRFs), have essential roles in specifying that satellite cells become skeletal muscle. It was hypothesized that three of these proteins (Pax7, Myf5, MyoD) have particularly important roles in providing this identity, due to their unique roles in activating the skeletal muscle program. Each was studied using a combination of molecular techniques, including genome-wide microarrays, PCR-based systems, protein assays, and immunostaining, to assess their effects on myoblast gene expression and function. In the absence of Pax7, adult myoblasts are lost through a p53-dependent pathway. Pax7 also regulates the expression of numerous genes in myoblasts, including Myf5. Alternative splicing within the Pax7 paired domain alters its ability to activate expression of target genes, including Myf5. Although Myf5 and MyoD are both expressed in growing myoblasts and are grossly redundant, MyoD uniquely primes myoblasts for differentiation through its divergent NH2- and COOH-terminal regions that flank the conserved bHLH domain. Therefore, Pax7, Myf5, and MyoD supply specific myogenic functions in satellite cells that provide for robust repair of injury to skeletal muscle tissue.