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First published online August 25, 2006
doi: 10.1242/10.1242/dev.02517

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The Wnt/ß-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis

Ugo Borello^1,2,*,, Barbara Berarducci^1,2, Paula Murphy³, Lola Bajard⁴, Viviana Buffa², Stefano Piccolo⁵, Margaret Buckingham⁴ and Giulio Cossu^1,6,

¹ Stem Cell Research Institute, Dibit, H. San Raffaele, Via Olgettina 58, 20132 Milan, Italy.
² Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Istologia ed Embriologia Medica, Universita di Roma `La Sapienza', Via A. Scarpa 14, 00161 Rome, Italy.
³ Zoology Department, Trinity College, Dublin 2, Ireland.
⁴ Department of Developmental Biology, CNRS URA 2578, Pasteur Institute, 25 Rue du Dr Roux, 75724 Paris Cedex 15, France.
⁵ Department of Histology, Microbiology and Medical Biotechnology, University of Padua, 35131 Padua, Italy.
⁶ Department of Biology, University of Milan, Via Celoria, 20133 Milan, Italy.

Authors for correspondence (e-mail: ugo.borello{at}ucsf.edu; cossu.giulio{at}hsr.it)

Accepted 3 July 2006

Canonical Wnt/ß-catenin signaling regulates the activation of the myogenic determination gene Myf5 at the onset of myogenesis, but the underlying molecular mechanism is unknown. Here, we report that the Wnt signal is transduced in muscle progenitor cells by at least two Frizzled (Fz) receptors (Fz1 and/or Fz6), through the canonical ß-catenin pathway, in the epaxial domain of newly formed somites. We show that Myf5 activation is dramatically reduced by blocking the Wnt/ß-catenin pathway in somite progenitor cells, whereas expression of activated ß-catenin is sufficient to activate Myf5 in somites but not in the presomitic mesoderm. In addition, we identified Tcf/Lef sequences immediately 5' to the Myf5 early epaxial enhancer. These sites determine the correct spatiotemporal expression of Myf5 in the epaxial domain of the somite, mediating the synergistic action of the Wnt/ß-catenin and the Shh/Gli pathways. Taken together, these results demonstrate that Myf5 is a direct target of Wnt/ß-catenin, and that its full activation requires a cooperative interaction between the canonical Wnt and the Shh/Gli pathways in muscle progenitor cells.

Key words: Myogenic induction, Myf5 activation, Wnt, ß-catenin, Frizzled, Sonic Hedgehog, Gli, Ep enhancer

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