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Publication : Regulation of vertebrate myotome development by the p38 MAP kinase-MEF2 signaling pathway.

First Author  de Angelis L Year  2005
Journal  Dev Biol Volume  283
Issue  1 Pages  171-9
PubMed ID  15890335 Mgi Jnum  J:99323
Mgi Id  MGI:3581988 Doi  10.1016/j.ydbio.2005.04.009
Citation  de Angelis L, et al. (2005) Regulation of vertebrate myotome development by the p38 MAP kinase-MEF2 signaling pathway. Dev Biol 283(1):171-9
abstractText  Biochemical and cell culture studies have characterized the myocyte enhancer factor 2 (MEF2) transcriptional regulatory proteins as obligatory partners for the myogenic regulatory factors (MRFs) in the differentiation of myogenic cells in culture. However, the role of MEF2 activation in somitic myogenesis has not been fully characterized. Here, we report a critical interaction between the p38 mitogen-activated protein kinase (p38 MAPK) and MEF2 in the developing somite myotome. We document expression of MEF2A and p38 MAPK proteins in the somite of 9.5 dpc mouse embryos concurrent with Myf 5 protein expression. We also observed that abrogation of p38 MAPK signaling blocks MEF2 activation using a MEF2 transgenic 'sensor' mouse. Inhibition of p38 MAPK signaling concurrently inhibited myogenic differentiation in somite cultures and in embryos in vivo using transplacental injection of a p38 inhibitor (SB203580). Finally, we document that commitment to the myogenic lineage is not appreciably affected by p38 MAPK inhibition since the activation of an early marker of myogenic commitment (Myf 5) occurs normally when p38 MAPK signaling is inhibited. Thus, we present novel evidence indicating a crucial role for p38 MAPK signaling to the MEF2 transcriptional regulators during early mammalian somite development and myotome formation.
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