GDNF/GFRα1 complex promotes 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 hippocampus remains unclear. In this work, we investigated the consequences of GFRα1 deficiency for the development of hippocampal connections. Analysis of conditional GFRα1-knockout mice shows a reduction in dendritic length and complexity, as well as a decrease in postsynaptic density (PSD) specializations and in the synaptic localization of postsynaptic proteins in hippocampal neurons. Gain and loss of function assays demonstrate that 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 GDNF/GFRα1 complex is essential for proper hippocampal circuit development.