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Science 8 August 2003:
Vol. 301. no. 5634, pp. 843 - 846
DOI: 10.1126/science.1085405
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Reports

Inhibition of Neuroepithelial Patched-Induced Apoptosis by Sonic Hedgehog

Chantal Thibert,1 Marie-Aimée Teillet,2 Françoise Lapointe,2 Laetitia Mazelin,1 Nicole M. Le Douarin,2 Patrick Mehlen1,3*

During early development in vertebrates, Sonic hedgehog (Shh) is produced by the notochord and the floor plate. A ventrodorsal gradient of Shh directs ventrodorsal patterning of the neural tube. However, Shh is also required for the survival of neuroepithelial cells. We show that Patched (Ptc) induces apoptotic cell death unless its ligand Shh is present to block the signal. Moreover, the blockade of Ptc-induced cell death partly rescues the chick spinal cord defect provoked by Shh deprivation. Thus, the proapoptotic activity of unbound Ptc and the positive effect of Shh-bound Ptc on cell differentiation probably cooperate to achieve the appropriate spinal cord development.

1 Apoptosis/Differentiation Laboratory, "La Ligue," Molecular and Cellular Genetic Center, CNRS Unite Mixte Recherche (UMR) 5534, University of Lyon, 69622 Villeurbanne, France.
2 Laboratoire d'Embryologie Cellulaire et Moléculaire, CNRS UMR 7128, 49 bis, Avenue de la Belle-Gabrielle, 94736 Nogent-sur-Marne Cedex, France.
3 International Agency for Research in Cancer, 69008 Lyon, France.

* To whom correspondence should be addressed. E-mail: mehlen{at}univ-lyon1.fr

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