GDNF/GFRa1 complex abrogates self-renewing activity of cortical neural precursors inducing their differentiation

BONAFINA, ANTONELA; MACARIA, DANILA; PARATCHA, GUSTAVO; LEDDA, FERNANDA

Mar del Plata

Congreso; XXXII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2017

Sociedad Argentina de Investigación en Neurociencias

he 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 GDNF/GFRα1 complex inhibits selfrenewal capacity of mouse cortical neural precursor cells induced by 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.