Netrin-1 is a survival factor during commissural neuron navigation.
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.
Furne
Céline
C
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.
Rama
Nicolas
N
Corset
Véronique
V
Chédotal
Alain
A
Mehlen
Patrick
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D016163:Genes, DCC / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D000075388:Netrin-1; D054259:Neural Tube / Q000196:embryology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D013116:Spinal Cord / Q000196:embryology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1
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