GDNF/GFR?1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation.

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 GFR?1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFR?1 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 GFR?1 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 GFR?1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFR?1-expressing neurons. Together, these results indicate that GDNF/GFR?1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors.

SUBMITTER: Bonafina A 

PROVIDER: S-EPMC5918270 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature