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First published online 27 May 2003
doi: 10.1242/jcs.00525

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Journal of Cell Science 116, 2885-2893 (2003)
doi: 10.1242/jcs.00525

Research Article

Inhibition of p38 MAPK signaling promotes late stages of myogenesis

Andrea D. Weston1,*, Arthur V. Sampaio1, Alan G. Ridgeway2,3 and T. Michael Underhill1,{ddagger}

1 Department of Physiology, Faculty of Medicine and Dentistry, The University of Western Ontario, London, Ontario, N6A 5C1, Canada
2 Department of Biochemistry, Faculty of Medicine and Dentistry, The University of Western Ontario, London, Ontario, N6A 5C1, Canada
3 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA

{ddagger} Author for correspondence (e-mail: tunderhi{at}uwo.ca)

Accepted 31 March 2003

Signaling through the p38 mitogen-activated protein kinases (MAPKs) is essential for cartilage formation in primary cultures of limb mesenchyme. Here we show that, concurrent with a decrease in chondrogenesis, inhibition of p38 in limb bud cultures dramatically promotes muscle development. Specifically, treatment of primary limb bud cultures with p38 inhibitors increases the expression of myogenic markers and causes a striking increase in formation of myotubes, which were detected using antibodies specific for myosin heavy chain. These results are surprising in that they contrast with several previous reports describing a requirement for p38 during myogenesis. Nonetheless, the enhanced myogenesis leads to the formation of an extensive network of contractile myofibers, and this enhanced myogenesis can be conferred upon myogenic cells from clonal populations, such as G8 or C2C12 cells, if they are co-cultured with the limb mesenchymal cells. We provide evidence for the maintenance and rapid organization of existing, somitic-derived limb myoblasts in response to p38 inhibitors. These findings imply a novel and unexpected role for p38 MAPK inhibition in myogenesis and highlight the importance of the limb bud microenvironment in promoting the progression of limb myoblasts.

Key words: Myogenesis, p38 MAPK, Limb mesenchyme, Chondrogenesis




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