Adult skeletal muscle is a very stable tissue containing a small population of 
myofiber-associated quiescent satellite cells compared with late 
embryonic/neonatal skeletal muscle, which contains highly proliferating 
myoblasts and small actively growing myofibers, suggesting that specific 
regulatory pathways may control myogenesis at distinct developmental stages. The 
p38 MAPK signaling pathway is central for myogenesis, based on studies using 
immortalized and neonatal primary myoblasts in vitro. However, the contribution 
of this pathway to adult myogenesis has never been investigated. Four p38 
isoforms (p38alpha, p38beta, p38gamma and p38delta) exist in mammalian cells, 
being p38alpha and p38gamma the most abundantly expressed isoforms in adult 
skeletal muscle. Given the embryonic/neonatal lethality of p38alpha-deficient 
mice, here we investigate the relative contribution of p38beta, p38gamma and 
p38delta to adult myogenesis. Regeneration and myofiber growth of adult muscle 
proceeds with similar efficiency in mice lacking p38beta, p38gamma and p38delta 
as in wild-type control mice. In agreement with this, there is no difference in 
adult primary myoblasts behavior in vitro among the different genotypes. 
Importantly, the pattern of p38 activation (ascribed to p38alpha) remains 
unperturbed during satellite cell-mediated myogenesis in vitro and adult muscle 
regeneration in wild type and p38beta-, p38gamma- and p38delta-deficient mice, 
rendering p38alpha as the essential p38 isoform sustaining adult myogenesis. 
This study constitutes the first analysis addressing the functionality of 
p38beta, p38gamma and p38delta in satellite cell-dependent adult muscle 
regeneration and growth.