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Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14465-70. doi: 10.1073/pnas.0803645105. Epub 2008 Sep 16.

Netrin-1 is a survival factor during commissural neuron navigation.

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Apoptosis, Cancer, and Development Laboratory, Equipe labellisée La Ligue, Centre Léon Berard and Unité Mixte de Recherche 5238, Centre National de la Recherche Scientifique, Université de Lyon, 69008 Lyon, France.


DCC (Deleted in Colorectal Cancer) is a putative tumor suppressor whose expression is lost in numerous cancers and whose tumor suppressor activity appears to be dependent on its ability to trigger apoptosis when disengaged by its ligand netrin-1. In this sense, netrin-1 is a survival factor that controls tumorigenesis. However, netrin-1 is also the prototypical axon guidance cue and has been shown to orient many neurons or axons, especially commissural axons, during spinal cord development. Here we show that netrin-1 is not only an attractive cue for developing commissural axons but also promotes their survival. In primary neuronal culture, in mice or in chick embryos, netrin-1 inhibits the proapoptotic activity of DCC in developing commissural neurons. Thus, adequate commissural neurons navigation requires both the attractive activity of netrin-1 and the anti-apoptotic function of this cue.

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