TGF-beta in cell fate decision of adult neural stem cells from the SVZ

ANA PAULA PIANTANIDA; PABLO RADICE; FERNANDO PITOSSI; PATRICIA MATHIEU

Congreso; Sociedad argentina de investigación en neurociencias; 2013

Adult NSC (aNSC) are able to differentiate into neurons, astrocytes and oligodendrocytes throughout life. Notch and transforming growth factor beta (TGF-beta) signaling pathways play critical roles in the control of cell fate. Previously it was demonstrated that TGF-beta is pro-neurogenic on hippocampal aNSC and it was reported that might interact with Notch pathway in different cellular types. Therefore the objective of our work is to study the effect of this cytokine on the generation of specific cell types from aNSC of the subventricular zone (SVZ) and its interaction with the Notch pathway. The addition of TGF-beta on aNSC cultures obtained from the SVZ of adult rats results in a 17.5% increase of the TujI positive population, whereas there were no changes in Nestin and GFAP positive population. This pro-neurogenic effect was also observed in vivo 21 days after the injection of an adenoviral vector expressing TGF-beta in the SVZ of adult Wistar rats. To study the participation of Notch pathway on this effect we performed real time PCR for Notch activation pathway reporter?s gens as Hes1 and Hey1. The presence of TGF-beta produced an increment in the Hes1 expression showing the activation of Notch pathway. Moreover, Hes1 expression increase was blocked by a gamma-secretase inhibitor. These data show that TGF-beta modulates the phenotype fate decision and preliminary results suggest that might also alters Notch pathway activation on these cultures.