TY - JOUR
T1 - Gdnf Activates Midline Repulsion by Semaphorin3B via NCAM during Commissural Axon Guidance
AU - Charoy, Camille
AU - Nawabi, Homaira
AU - Reynaud, Florie
AU - Derrington, Edmund
AU - Bozon, Muriel
AU - Wright, Kevin
AU - Falk, Julien
AU - Helmbacher, Françoise
AU - Kindbeiter, Karine
AU - Castellani, Valérie
N1 - Funding Information:
We thank David Ginty for sharing of RET mouse lines (RET fwnt1 and RET-CFP) and comments on the manuscript, Fritz Rathjen for the gift of the NrCAM mouse line, Geneviève Rougon for the gift of the NCAM mouse line, and Josh Sanes for the gift of the Sema3B mouse line. The gdnf mouse line was provided by Genentech. This work was supported by grants from the National Agency for Research (ANR, ANR-2010-BLANC-1430-01), the Fondation pour la Recherche Médicale (FRM) Label Team Program, and the Labex DevWeCan (ANR-10-LABX-61) to V.C.
PY - 2012/9/20
Y1 - 2012/9/20
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2012.08.021
DO - 10.1016/j.neuron.2012.08.021
M3 - Article
C2 - 22998873
AN - SCOPUS:84866503317
SN - 0896-6273
VL - 75
SP - 1051
EP - 1066
JO - Neuron
JF - Neuron
IS - 6
ER -