GFRα1 Regulates Purkinje Cell Migration by Counteracting NCAM Function

Publication date: 10 January 2017
Source:Cell Reports, Volume 18, Issue 2
Author(s): Maria Christina Sergaki, Carlos F. Ibáñez
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 NCAM is co-expressed and directly interacts with GFRα1 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 GFRα1 can function both in cis and trans to counteract NCAM and promote PC migration. Collectively, our studies show that GFRα1 contributes to PC migration by limiting NCAM function.

Graphical abstract

Teaser

During embryonic development of the cerebellum, Purkinje cells migrate away from the ventricular zone (VZ) to form a monolayer. Sergaki and Ibáñez show that the neurotrophic receptor GFRα1 regulates Purkinje cell migration by limiting the function of the neural cell adhesion molecule NCAM.


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