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

First Author  Charoy C Year  2012
Journal  Neuron Volume  75
Issue  6 Pages  1051-66
PubMed ID  22998873 Mgi Jnum  J:188327
Mgi Id  MGI:5440338 Doi  10.1016/j.neuron.2012.08.021
Citation  Charoy C, et al. (2012) gdnf Activates Midline Repulsion by Semaphorin3B via NCAM during Commissural Axon Guidance. Neuron 75(6):1051-66
abstractText  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/GFRalpha1 signaling. This study identifies a regulator of midline crossing and reveals interplays between Semaphorin and gdnf signaling during axon guidance.
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