Regulation of Neuronal Development by Growth Factors: ?In vivo? studies

NIETO GUIL, A.; NIETO, M.; QUIROGA, S.

Mar del Plata

Congreso; XXX Congreso de la Sociedad Argentina de Investigaciones en Neurociencias (SAN); 2015

SAN

The cerebral cortex, experiences arapid expansion at early stages of development, resulting in the formation ofsix horizontal layers, each containing distinct neuronal populations exhibitingdifferent biochemical and functional characteristics. This development requiresthe coordinated of several processes, such as symmetric and asymmetric divisionof progenitor cells at the ventricular zone (VZ).Neuronal migration to fill specificareas of the neo-cortex, and specification neuron polarization leading to dendriticand axonal development. Using ?in utero?electroporation (IUE) we studied the consequences of blocking two different receptor-growthfactor systems on cerebral cortex formation: i)The IGF-1 receptor (IGF-1R) systeminvolved in neuronal differentiation and the establishment of polarity¸ and ii)transforminggrowth factor β (TGF-β)-TGF-β receptors(TGF-βR), also shown to be important for the establishment of neuronalpolarity. The result shows that knocking down the IGF-1R in arrested corticalneurons at the VZ and resulted in heterotopic like structures. This phenotypewas partially rescued by over expressing P110, a kinase known to act downstreamof the IGF-1R. Silencing the TGF-βR resulted in a subpopulation of neuronsdelayed in the intermedia zone (IZ) of the cortex and a small cohort of lateborn neurons abnormally stalled at the upper layer V. The results demonstratethe critical participation of the two receptors at different stages of neuronaldeveloped.