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Development. 2016 Nov 15;143(22):4224-4235. Epub 2016 Oct 5.

The GDNF-GFRα1 complex promotes the development of hippocampal dendritic arbors and spines via NCAM.

Author information

1
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.
2
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.

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.

KEYWORDS:

Dendrite complexity; Dendritic spines; GDNF; Hippocampus; Mouse; NCAM; Rat; Structural plasticity

PMID:
27707798
DOI:
10.1242/dev.140350
[Indexed for MEDLINE]
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