Gdnf/gfra1 regulates cell proliferation and differentiation of cortical progenitors

ANTONELA BONAFINA; PAULA FONTANET; FERNANDO CRUZ ALSINA; GUSTAVO PARATCHA; FERNANDA LEDDA

Cordoba

Congreso; Congreso de la Sociedad Argentina de Neurociencias (SAN); 2013

Sociedad Argentina de Neurociencias (SAN)

Glial cell line-derived neurotrophic factor (GDNF) was initially discovered as a survival factor for midbrain dopaminergic neurons. GDNF signals by binding to the glycosylphosphatidylinositol-anchored receptor GFRa1 in complex with the receptor tyrosine kinase Ret or the neural cell adhesion molecule (NCAM). In addition to midbrain dopaminergic neurons, GFRa1 is expressed by several different classes of neurons in the central and peripheral nervous system, indicating that GDNF has broader actions than initially proposed. As GDNF and its receptor GFRa1 has been described to be expressed at early developmental stages in the forebrain, we asked whether GDNF signaling trough its GFRa1 receptor is important for embryonic forebrain precursor cell development. Interestingly, reverse transcription analysis of total RNA isolated from forebrain precursors maintained in proliferating conditions shows lower levels of GFRα1 expression than precursors maintained in differentiating conditions showing a clear correlation between GFRa1 expression and neuronal differentiation. Addition of GDNF to proliferating precursors resulted in the inhibition of neuronal precursor proliferation and in a significant increase in neuritic branch complexity and length of the differentiated neurons. Thus, our results indicate that GDNF/GFRa1 signaling plays an essential role controlling the transition of the neuronal progenitors from a proliferative condition towards neuronal differentiation. GDNF/GFRa1 signaling might be playing an essential role in the regulation of the proliferative condition of neuronal cortical progenitors