Wnt3a triggers polarization of hippocampal neurons via activation of th IGF-1 receptor/PI3K pathway

BERNIS, ME; DUPRAZ, S; QUIROGA S; ROSSO SB

Huerta Grande- Córdoba

Congreso; XXVI Congreso Annual de la Sociedad Argentina de Investigación en Neurociencia.; 2011

Sociedad Argentina de Neurociencia

The selection of the future axon in cultured hippocampal neuron requires the activation of IGF-1 receptor (IGF-1R), PI3k and the accumulation of PIP3 at the growth cone. Neuronal polarization is regulated by a combination of intrinsic programs of gene expression and by extrinsic factors as Wnts and IGF-1. Wnts, through Frizzled receptors, activate Dishevelled (Dvl), a first downstream effector that can signal through different pathways. In the nervous system, Wnt function as a regulator of neuronal development. We studied Wnt3a on neuronal differentiation, particularly on the regulation of axonal outgrowth. We observed that Wnt3a is necessary for axon formation through the activation of PI3k. Neurons cultured in the presence of Wnt3a or overexpressing Dvl show multiple axons. Importantly, Wnt3a activates PI3k in neurons and in purified growth cones suggesting that Wnt3a may signals through the same pathway as IGF-1/IGF-1R. In addition, we found that Wnt3a cross-activates IGF-1R in neurons and in growth cones and this effect is blocked by an IGF-1R blocking antibody. These findings suggest that Wnt proteins are important for the establishment of neuronal polarity and suggest a possible parallelism between the two signalling systems: Wnt-Fz-DVL and IGF-1-IGFR-PI3k on axon formation.