gdnf Activates Midline Repulsion by Semaphorin3B via NCAM during Commissural Axon Guidance.

Camille Charoy (1) , Homaira Nawabi (1) , Florie Reynaud (1) , Edmund Derrington (1, 2) , Muriel Bozon (1) , Kevin Wright (3) , Julien Falk (1) , Françoise Helmbacher (4) , Karine Kindbeiter (1, 5) , Valérie Castellani (1)

1 CGPhiMC - Centre de génétique et de physiologie moléculaire et cellulaire
2 Virologie humaine
3 HHMI - Howard Hughes Medical Institute
4 IBDML - Institut de Biologie du Développement de Marseille-Luminy
5 Idéalp' Pharma

The Neurotrophic factor gdnf plays diverse developmental roles, supporting survival and also acting as a chemoattractant for axon and cell migration. We report that in the developing spinal cord, a focal source of gdnf is present in the floor plate (FP) where commissural axons cross the midline. Gdnf has no direct guidance properties but switches on the responsiveness of crossing commissural growth cones to the midline repellent Semaphorin3B by suppressing calpain-mediated processing of the Sema3B signaling coreceptor Plexin-A1. Analysis of single and double mutant mouse models indicates that although gdnf is the principal trigger of Sema3B midline repulsion, it acts with another FP cue, NrCAM. Finally, genetic and in vitro experiments provide evidence that this gdnf effect is RET independent and mediated by NCAM/GFRα1 signaling. This study identifies a regulator of midline crossing and reveals interplays between Semaphorin and gdnf signaling during axon guidance.

Domaines: Biochimie, Biologie Moléculaire; Biologie cellulaire

Camille Charoy, Homaira Nawabi, Florie Reynaud, Edmund Derrington, Muriel Bozon, et al.. gdnf Activates Midline Repulsion by Semaphorin3B via NCAM during Commissural Axon Guidance.. Neuron, 2012, 75 (6), pp.1051-66. ⟨10.1016/j.neuron.2012.08.021⟩. ⟨hal-00749612⟩