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First published online 14 November 2006
doi: 10.1242/jcs.03278

Journal of Cell Science 119, 4828-4840 (2006)
Published by The Company of Biologists 2006
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Research Article

Convergence of Igf2 expression and adhesion signalling via RhoA and p38 MAPK enhances myogenic differentiation

Fiona A. Lovett1, Ivelisse Gonzalez1, Dervis A. M. Salih1, Laura J. Cobb1, Gyanendra Tripathi1, Ruth A. Cosgrove1, Adele Murrell2, Peter J. Kilshaw1 and Jennifer M. Pell1,*

1 The Babraham Institute, Babraham Research Campus, Cambridge, CB2 4AT, UK
2 Department of Oncology, Cambridge University, MRC-Hutchison Centre, Cambridge, CB2 2XZ, UK

* Author for correspondence (e-mail: jenny.pell{at}bbsrc.ac.uk)

Accepted 25 September 2006

Cell-cell contact is essential for appropriate co-ordination of development and it initiates significant signalling events. During myogenesis, committed myoblasts migrate to sites of muscle formation, align and form adhesive contacts that instigate cell-cycle exit and terminal differentiation into multinucleated myotubes; thus myogenesis is an excellent paradigm for the investigation of signals derived from cell-cell contact. PI3-K and p38 MAPK are both essential for successful myogenesis. Pro-myogenic growth factors such as IGF-II activate PI3-K via receptor tyrosine kinases but the extracellular cues and upstream intermediates required for activation of the p38 MAPK pathway in myoblast differentiation are not known. Initial observations suggested a correlation between p38 MAPK phosphorylation and cell density, which was also related to N-cadherin levels and Igf2 expression. Subsequent studies using N-cadherin ligand, dominant-negative N-cadherin, constitutively active and dominant-negative forms of RhoA, and MKK6 and p38 constructs, reveal a novel pathway in differentiating myoblasts that links cell-cell adhesion via N-cadherin to Igf2 expression (assessed using northern and promoter-reporter analyses) via RhoA and p38{alpha} and/or ß but not {gamma}. We thus define a regulatory mechanism for p38 activation that relates cell-cell-derived adhesion signalling to the synthesis of the major fetal growth factor, IGF-II.

Key words: Cadherin, Cell-cell contact, IGF-II, Myogenic differentiation, p38 MAPK, RhoA


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[Abstract] [Full Text] [PDF]


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