First Author | Sergaki MC | Year | 2017 |
Journal | Cell Rep | Volume | 18 |
Issue | 2 | Pages | 367-379 |
PubMed ID | 28076782 | Mgi Jnum | J:251552 |
Mgi Id | MGI:6103001 | Doi | 10.1016/j.celrep.2016.12.039 |
Citation | Sergaki MC, et al. (2017) GFRalpha1 Regulates Purkinje Cell Migration by Counteracting NCAM Function. Cell Rep 18(2):367-379 |
abstractText | 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 GFRalpha1 is transiently expressed in developing PCs and loss of GFRalpha1 delays PC migration. Neither GDNF nor RET, the canonical GFRalpha1 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 GFRalpha1 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 GFRalpha1 can function both in cis and trans to counteract NCAM and promote PC migration. Collectively, our studies show that GFRalpha1 contributes to PC migration by limiting NCAM function. |