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

[en] 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.

Disciplines :

Anatomy (cytology, histology, embryology...) & physiology

Author, co-author :

Irala, Dolores

Bonafina, Antonela ; Université de Liège - ULiège > Stem Cells-Molecular Regulation of Neurogenesis

Fontanet, Paula Aldana

Alsina, Fernando Cruz

Paratcha, Gustavo

Ledda, Fernanda

Language :

English

Title :

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

Publication date :

2016

Journal title :

Development (Cambridge, England)

ISSN :

0950-1991

eISSN :

1477-9129

Volume :

143

Issue :

Pages :

4224-4235

Peer reviewed :

Peer reviewed

Commentary :

Available on ORBi :

since 08 June 2020

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