CONICET | Buscador de Institutos y Recursos Humanos

The selection of the future axon in cultured hippocampal neuron requires the activation of IGF-1 receptor (lGF-1 r), Pf3k and the accumulation of PIP3 at the growth cone (Shi et al., 2003; Menager et aI., 2004; Sosa et al., 2006). Growth factors belonging to the Wnts family have been also implied in the regulation of axonal development (Arevalo and Chao, 2005). It is not known, however, if Wnts have any participation in the regulation of initial axonal outgrowth and the establishment of neuronal polarity. We used cultured hippocampal pyramidal neurons and growth cone particles (GCPs) isolated from fetal rat brain to show that stimulation with Wnt3a is sufficient to trigger neuronal polarization in the absence of IGF-1 or a high level of insulin. We also show that Wnt3a triggers the activation of IGF-1r and PI3k (polarized to one minor neurite) in neurons in stage 2 of development. In addition, we show that the presence of activatable IGF1r and PI3k activation are necessary for Wnt3a polarizing effects. Finally, using crosslinking and immunoprecipitation experiments, we show that Wnt3a directly binds to IGF-1 r. We conclude that Wnt3a triggers polarization of hippocampal neurons via direct activation of the IGF-1 r/PI3k pathway.