Role of p53 family members during development of striated muscle, with focus on p63.

Background: During vertebrate development, p53 family members (p53, p63, and p73) play both discrete and redundant roles. While p63 gene mutations lead to various skeletal and organ birth defects, p63's role in muscle development is less considered. Muscles derive from embryonic mesoderm. However, head and heart muscle differentiation also depends on intrinsic cues and signals from adjacent epithelia. In p63 mutant mice, ectoderm- and endoderm-derived epithelia are defective, implying defective myogenesis. We review the evidence that p63 is important for the differentiation of striated muscles, including cardiopharyngeal field-derived head and heart musculature.

Results: Several p63 isoforms act during mesoderm induction, myoblast proliferation, cell cycle exit, and cell differentiation. Of particular interest, TAp63γ is expressed in embryonic myoblasts and endoderm. In striated muscles, TAp63γ functions in myogenic proliferation and differentiation and participates in sarcomere development and myofibril assembly.

Conclusions: p63 is active during all muscle development stages, from mesoderm induction to myocyte differentiation. Different p53 family members, including several p63 isoforms, have overlapping functions. This redundancy could explain the limited myopathies described in p63 mouse mutants. As these defects may be subtler and more age/stage-dependent than appreciated, they warrant further study.