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© The Rockefeller University Press, 0021-9525/2003/6/835-a $5.00
The Journal of Cell Biology, Volume 161, Number 5, 835-a-835

A cytokine that packs a punch

Nascent myotubes (green) grow by IL-4–mediated fusion with myoblasts (red). Pavlath

Muscle cells undergo an unusual developmental program in which several partially differentiated cells called myoblasts fuse to form a multinucleated myotube. This nascent myotube undergoes further maturation and growth, which requires the addition of nuclei by fusion of more mononucleated myoblasts with myotubes. Valerie Horsley, Grace Pavlath, and colleagues (Emory University, Atlanta, Georgia) have found that nascent myotubes promote fusion, and thus their own growth, by secreting a cytokine normally associated with immune cells.

The cross-system cytokine is IL-4, which is required in immune cells for macrophage fusion. Not one to throw away a good thing, Nature evidently coopted the system for muscle cells. As in immune cells, IL-4 expression in nascent myotubes is driven by a member of the NFAT transcription factor family. Myotubes lacking either IL-4 or the NFAT factor were smaller and had fewer nuclei than wild-type cells. Recovery from muscle injury was also diminished by the lack of IL-4 or the IL4 receptor.

Myoblasts are the targets of IL-4 action, which may promote fusion by inducing myoblast expression of adhesion molecules such as integrins (as in macrophages) or VCAM. Alternatively, IL-4 may act as a chemokine, as it does for osteoblasts, to stimulate migration of myoblasts toward myotubes. Whatever the mechanism, stem cell therapies for disorders such as muscular dystrophies may be improved by expression of IL-4 to increase the fusion capacity of the muscle stem cells.

Reference:

Horsley, V., et al. 2003. Cell. 113:483–494.[CrossRef][Medline]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 695K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?