title: The GDNF-GFRα1 complex promotes the development of hippocampal dendritic arbors and spines via NCAM.
abstract: The formation of synaptic connections during nervous system development requires the precise control of dendrite growth and synapse formation. Although glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRα1 are expressed in the forebrain, the role of this system in the hippocampus remains unclear. Here, we investigated the consequences of GFRα1 deficiency for the development of hippocampal connections. Analysis of conditional Gfra1 knockout mice shows a reduction in dendritic length and complexity, as well as a decrease in postsynaptic density specializations and in the synaptic localization of postsynaptic proteins in hippocampal neurons. Gain- and loss-of-function assays demonstrate that the GDNF-GFRα1 complex promotes dendritic growth and postsynaptic differentiation in cultured hippocampal neurons. Finally, in vitro assays revealed that GDNF-GFRα1-induced dendrite growth and spine formation are mediated by NCAM signaling. Taken together, our results indicate that the GDNF-GFRα1 complex is essential for proper hippocampal circuit development.
authors.affiliation: Division of Molecular and Cellular Neuroscience, Institute of Cell Biology and Neuroscience (IBCN)-CONICET, School of Medicine, University of Buenos Aires (UBA), Buenos Aires 1121, Argentina.
authors.forename: Dolores
authors.initials: D
authors.lastname: Irala
authors.affiliation: Division of Molecular and Cellular Neuroscience, Institute of Cell Biology and Neuroscience (IBCN)-CONICET, School of Medicine, University of Buenos Aires (UBA), Buenos Aires 1121, Argentina.
authors.forename: Antonela
authors.initials: A
authors.lastname: Bonafina
authors.affiliation: Division of Molecular and Cellular Neuroscience, Institute of Cell Biology and Neuroscience (IBCN)-CONICET, School of Medicine, University of Buenos Aires (UBA), Buenos Aires 1121, Argentina.
authors.forename: Paula Aldana
authors.initials: PA
authors.lastname: Fontanet
authors.affiliation: Division of Molecular and Cellular Neuroscience, Institute of Cell Biology and Neuroscience (IBCN)-CONICET, School of Medicine, University of Buenos Aires (UBA), Buenos Aires 1121, Argentina.
authors.forename: Fernando Cruz
authors.initials: FC
authors.lastname: Alsina
authors.affiliation: Division of Molecular and Cellular Neuroscience, Institute of Cell Biology and Neuroscience (IBCN)-CONICET, School of Medicine, University of Buenos Aires (UBA), Buenos Aires 1121, Argentina.
authors.forename: Gustavo
authors.identifier: 0000-0002-0804-4433
authors.initials: G
authors.lastname: Paratcha
authors.affiliation: Division of Molecular and Cellular Neuroscience, Institute of Cell Biology and Neuroscience (IBCN)-CONICET, School of Medicine, University of Buenos Aires (UBA), Buenos Aires 1121, Argentina mledda@fmed.uba.ar.
authors.forename: Fernanda
authors.identifier: 0000-0002-9769-6926
authors.initials: F
authors.lastname: Ledda
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D004622:Embryo, Mammalian; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000502:physiology; D009415:Nerve Net / Q000254:growth & development / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar
chemical_list: C495040:Gdnf protein, mouse; C494988:Gfra1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D046912:Multiprotein Complexes; D019006:Neural Cell Adhesion Molecules
keywords: Dendrite complexity; Dendritic spines; GDNF; Hippocampus; Mouse; NCAM; Rat; Structural plasticity