GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation

Stem Cell Reports
Antonela BonafinaFernanda Ledda

Abstract

The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs) determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2), promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors.

Citations

May 15, 2020·Experimental Neurobiology·Dongyoung YunSang Ryong Kim
Aug 2, 2020·Cell and Tissue Research·Carlos F IbáñezFernanda Ledda
Jan 23, 2021·Molecular Neurobiology·Kouminin KanworeDianshuai Gao
Jun 8, 2021·Frontiers in Neuroscience·Massimo M OnestoTimothy M Gomez

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