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Published online 1 November 2004. doi:10.1083/jcb.200405039
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 3, 493-504
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Article

 Netrins and neogenin promote myotube formation

Jong-Sun Kang, Min-Jeong Yi, Wei Zhang, Jessica L. Feinleib, Francesca Cole, and Robert S. Krauss

Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029

Correspondence to Robert S. Krauss: Robert.Krauss{at}mssm.edu

Differentiation of skeletal myoblasts into multinucleated myotubes is a multistep process orchestrated by several families of transcription factors, including myogenic bHLH and NFAT proteins. The activities of these factors and formation of myotubes are regulated by signal transduction pathways, but few extracellular factors that might initiate such signals have been identified. One exception is a cell surface complex containing promyogenic Ig superfamily members (CDO and BOC) and cadherins. Netrins and their receptors are established regulators of axon guidance, but little is known of their function outside the nervous system. We report here that myoblasts express the secreted factor netrin-3 and its receptor, neogenin. These proteins stimulate myotube formation and enhance myogenic bHLH- and NFAT-dependent transcription. Furthermore, neogenin binds to CDO in a cis fashion, and myoblasts lacking CDO are defective in responding to recombinant netrin. It is proposed that netrin-3 and neogenin may promote myogenic differentiation by an autocrine mechanism as components of a higher order complex of several promyogenic cell surface proteins.

Abbreviations used in this paper: ß-gal, ß-galactosidase; DM, differentiation medium; FNIII, fibronectin type III; GM, growth medium; MHC, myosin heavy chain; TnT, troponin T.


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