Role of GDNF/GFRα1 in the regulation of the proliferation and differentiation of neuronal cortical progenitors

BONAFINA, A; FONTANET, P; IRALA, D; PARATCHA G; LEDDA, F

Congreso; Congreso Anual de la Sociedad Argentina de Investigación BIoquímica y Biología Celular; 2014

The generation of differentiated neurons and glial cells from proliferating neural stem or progenitors cells is a complex process involving an interplay between intrinsic cellular programs and extrinsic cues such as trophic factors. This process has been well studied in the developing cortex, where stem and progenitors cells proliferate within the cortical ventricular zone and then differentiate into neurons. Cultured embryonic cortical progenitor cells mimic the temporal differentiation pattern observed in vivo. Study of this system has led to the identification of FGF2 as an essential survival and proliferating factor for cortical progenitors both in vivo and in vitroGlial cell line-derived neurotrophic factor (GDNF) was originally discovered because of its ability to promote the survival of ventral midbrain dopaminergic neurons. GDNF signals by binding to the glycosylphosphatidylinositol-anchored receptor GFRα1 in complex with the canonic receptor tyrosine kinase Ret or the neural cell adhesion molecule (NCAM). GDNF and its receptor GFRα1 have been reported to have an essential role in cell migration and differentiation in the peripheral and central nervous system. In particular, GDNF can stimulate migration of precursors of inhibitory interneurons in the rostral migratory stream, and the cerebral cortex. However the role of GDNF/ GFRα1 in the forebrain development is still unknown.