gdnf activates midline repulsion by Semaphorin3B via NCAM during commissural axon guidance

Camille Charoy; Homaira Nawabi; Florie Reynaud; Edmund Derrington; Muriel Bozon; Kevin Wright; Julien Falk; Françoise Helmbacher; Karine Kindbeiter; Valérie Castellani

doi:10.1016/j.neuron.2012.08.021

gdnf activates midline repulsion by Semaphorin3B via NCAM during commissural axon guidance

Neuron. 2012 Sep 20;75(6):1051-66. doi: 10.1016/j.neuron.2012.08.021.

Authors

Camille Charoy¹, Homaira Nawabi, Florie Reynaud, Edmund Derrington, Muriel Bozon, Kevin Wright, Julien Falk, Françoise Helmbacher, Karine Kindbeiter, Valérie Castellani

Affiliation

¹ University of Lyon, University Claude Bernard Lyon1, CGphiMC UMR CNRS 5534, 69622 Villeurbanne, France.

PMID: 22998873
DOI: 10.1016/j.neuron.2012.08.021

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
Axons / drug effects
Axons / physiology*
Body Patterning / genetics
Calpain / metabolism
Cell Movement / drug effects
Cell Movement / genetics
Cells, Cultured
Embryo, Mammalian
Gene Expression Regulation, Developmental / drug effects
Gene Expression Regulation, Developmental / genetics
Gene Expression Regulation, Developmental / physiology*
Glial Cell Line-Derived Neurotrophic Factor / deficiency
Glial Cell Line-Derived Neurotrophic Factor / metabolism*
Glial Cell Line-Derived Neurotrophic Factor / pharmacology
Humans
Mice
Mice, Transgenic
Nerve Tissue Proteins / metabolism
Neural Cell Adhesion Molecules / genetics
Neural Cell Adhesion Molecules / metabolism*
Neurons / cytology*
Neurons / drug effects
Receptors, Cell Surface / metabolism
Semaphorins / genetics
Semaphorins / metabolism*
Spinal Cord / cytology
Spinal Cord / embryology
Transfection

Substances

Glial Cell Line-Derived Neurotrophic Factor
Nerve Tissue Proteins
Neural Cell Adhesion Molecules
Plxna1 protein, mouse
Receptors, Cell Surface
Semaphorins
Calpain