title: GFRα1 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 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.
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm 17177, Sweden.
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Sergaki
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm 17177, Sweden; Department of Physiology, National University of Singapore, Singapore 117597, Singapore; Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore. Electronic address: carlos.ibanez@ki.se.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Ibáñez
mesh_terms: D000818:Animals; D002465:Cell Movement; D002531:Cerebellum / Q000166:cytology; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D019006:Neural Cell Adhesion Molecules; D051096:Proto-Oncogene Proteins c-ret
keywords: GDNF; RET; cell adhesion; cerebellum; development