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© The Rockefeller University Press, 0021-9525/1997//145 $5.00
The Journal of Cell Biology, Volume 139, Number 1, , 1997 145-156


Article

Positive and Negative Regulation of Muscle Cell Identity by Members of the hedgehog and TGF-β Gene Families



Shao Jun Du*, Stephen H. Devoto{ddagger}, Monte Westerfield{ddagger}, and Randall T. Moon*

* Howard Hughes Medical Institute and Department of Pharmacology, University of Washington, School of Medicine, Seattle, Washington 98195; and {ddagger} Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403

We have examined whether the development of embryonic muscle fiber type is regulated by competing influences between Hedgehog and TGF-β signals, as previously shown for development of neuronal cell identity in the neural tube. We found that ectopic expression of Hedgehogs or inhibition of protein kinase A in zebrafish embryos induces slow muscle precursors throughout the somite but muscle pioneer cells only in the middle of the somite. Ectopic expression in the notochord of Dorsalin-1, a member of the TGF-β superfamily, inhibits the formation of muscle pioneer cells, demonstrating that TGF-β signals can antagonize the induction of muscle pioneer cells by Hedgehog. We propose that a Hedgehog signal first induces the formation of slow muscle precursor cells, and subsequent Hedgehog and TGF-β signals exert competing positive and negative influences on the development of muscle pioneer cells.


Abbreviations used in this paper: β-gal, β-galactosidase; bGFP, bright green fluorescence protein; PKA, protein kinase A; twhh, tiggy-winkle hedgehog..

Address all correspondence to Randall T. Moon, Howard Hughes Medical Institute, Box 35370, Room K536C HSB, University of Washington, Seattle, WA 98195. Tel.: (206) 543-1722. Fax: (206) 616-4230. e-mail: rtmoon{at}u.washington.edu

Shao Jun Du and Stephen H. Devoto contributed equally to the project.



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