A role for p38alpha mitogen-activated protein kinase in embryonic cardiac differentiation.

Cardiac differentiation involves cross-regulation of several transcription factors, such as Mef2C, regulated by p38alpha MAP kinase. We analysed the role of p38alpha in cardiac differentiation. Either the absence or inhibition of p38alpha impairs MEF2C nuclear localization in cardiomyocytes, colocalising with vimentin at the perinuclear region. As a consequence, expression of the Mef2C targets, ANF and myocardin, is drastically downregulated. In contrast, Mlc2v and crt are mainly unaltered, probably by the strong Mef2B upregulation, conpensating for the impaired Mef2C transactivity. In addition, p38alpha deficiency leads to a decrease in the phosphorylated Mlc2v fraction and alpha-actinin accumulation causing sarcomere disorganisation. We propose a critical role for p38alpha in early stages of cardiac differentiation by modulation of Mef2C localisation and sarcomeric assembly.