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

First Author  Irala D Year  2016
Journal  Development Volume  143
Issue  22 Pages  4224-4235
PubMed ID  27707798 Mgi Jnum  J:240475
Mgi Id  MGI:5883653 Doi  10.1242/dev.140350
Citation  Irala D, et al. (2016) The GDNF-GFRalpha1 complex promotes the development of hippocampal dendritic arbors and spines via NCAM. Development 143(22):4224-4235
abstractText  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 GFRalpha1 are expressed in the forebrain, the role of this system in the hippocampus remains unclear. Here, we investigated the consequences of GFRalpha1 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-GFRalpha1 complex promotes dendritic growth and postsynaptic differentiation in cultured hippocampal neurons. Finally, in vitro assays revealed that GDNF-GFRalpha1-induced dendrite growth and spine formation are mediated by NCAM signaling. Taken together, our results indicate that the GDNF-GFRalpha1 complex is essential for proper hippocampal circuit development.
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