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GFR?1 Regulates Purkinje Cell Migration by Counteracting NCAM Function.

ABSTRACT: During embryonic development of the cerebellum, Purkinje cells (PCs) migrate away from the ventricular zone to form the PC plate. The mechanisms that regulate PC migration are incompletely understood. Here, we report that the neurotrophic receptor GFR?1 is transiently expressed in developing PCs and loss of GFR?1 delays PC migration. Neither GDNF nor RET, the canonical GFR?1 ligand and co-receptor, respectively, contribute to this process. Instead, we found that the neural cell adhesion molecule NCAM is co-expressed and directly interacts with GFR?1 in embryonic PCs. Genetic reduction of NCAM expression enhances wild-type PC migration and restores migration in Gfra1 mutants, indicating that NCAM restricts PC migration in the embryonic cerebellum. In vitro experiments indicated that GFR?1 can function both in cis and trans to counteract NCAM and promote PC migration. Collectively, our studies show that GFR?1 contributes to PC migration by limiting NCAM function.

SUBMITTER: Sergaki MC

PROVIDER: S-EPMC5263233 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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GFRα1 Regulates Purkinje Cell Migration by Counteracting NCAM Function.

Sergaki Maria Christina MC Ibáñez Carlos F CF

Cell reports 20170101 2

During embryonic development of the cerebellum, Purkinje cells (PCs) migrate away from the ventricular zone to form the PC plate. The mechanisms that regulate PC migration are incompletely understood. Here, we report that the neurotrophic receptor GFRα1 is transiently expressed in developing PCs and loss of GFRα1 delays PC migration. Neither GDNF nor RET, the canonical GFRα1 ligand and co-receptor, respectively, contribute to this process. Instead, we found that the neural cell adhesion molecule ...[more]

PMID: 28076782

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