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GENES & DEVELOPMENT 22:1828-1837, 2008
©2008 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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Pax3 regulation of FGF signaling affects the progression of embryonic progenitor cells into the myogenic program

Mounia Lagha1, Jay D. Kormish1,3, Didier Rocancourt, Marie Manceau4, Jonathan A. Epstein5, Kenneth S. Zaret3, Frédéric Relaix2, and Margaret E. Buckingham6

CNRS URA 2578, Department of Developmental Biology, Pasteur Institute, 75015 Paris, France

Pax3/7-dependent stem cells play an essential role in skeletal muscle development. We now show that Fgfr4 lies genetically downstream from Pax3 and is a direct target. In chromatin immunoprecipitation (ChIP)-on-chip experiments, Pax3 binds to a sequence 3' of the Fgfr4 gene that directs Pax3-dependent expression at sites of myogenesis in transgenic mouse embryos. The activity of this regulatory element is also partially dependent on E-boxes, targets of the myogenic regulatory factors, which are expressed as progenitor cells enter the myogenic program. Other FGF signaling components, notably Sprouty1, are also regulated by Pax3. In vivo manipulation of Sprouty expression reveals that FGF signaling affects the balance between Pax-positive progenitor cells and committed myoblasts. These results provide new insight into the Pax-initiated regulatory network that modulates stem cell maintenance versus tissue differentiation.

[Keywords: Pax3; Fgfr4; Sprouty1; myogenesis; embryonic ChIP-on-chip; somite; skeletal muscle progenitor cells]

Received February 28, 2008; revised version accepted May 9, 2008.

1 These authors contributed equally to this work.

2 Present addresses: UMR S 787, INSERM-UPMC-Paris VI, Faculté de Médecine Pitié-Salpétrière, 75634 Paris, France;

3 Cell and Developmental Biology Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA;

4 IBDM, Université de la Méditerranée, CNRS, UMR 6216, Campus de Luminy, Case 907, 13288 Marseille, France;

5 Department of Cell and Developmental Biology, University of Pennsylvania, 1154 BRB II, 421 Curie Boulevard, Philadelphia, PA 19104, USA.

6 Corresponding author.

E-MAIL margab{at}pasteur.fr; FAX 331-40-613452.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.477908.


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