Signaling involved in neurite outgrowth of postnatally born subventricular zone neurons in vitro

Background: Neurite outgrowth is a key process during neuronal migration and differentiation. Complex intracellular signaling is involved in the initiation of neurite protrusion and subsequent elongation. Although, in general many constituents of the machinery involved in this multi-stage process are common for neurons in distinct brain areas, there are notable differences between specific neuronal subtypes. Results: We analyzed key intracellular components of neurite outgrowth signaling in postnatally born subventricular zone (SVZ) neurons in vitro. We showed that inhibitors of PI3K, Akt1, PKC zeta and small GTPases significantly reduced neurite outgrowth. Transfection of SVZ-derived neurons with inactive forms of Rac1 or Cdc42 also decreased neurite length whereas transfection with constitutively active forms of Rac1, Cdc42 or Akt1 as well as with full-length PI3K or PKC zeta increased neurite length. PI3K, Akt1 and PKC zeta acted upstream of the small GTPases Rac1 and Cdc42, which in turn modulate lamellipodia formation of SVZ-derived neurons. Conclusion: We showed the involvement of PI3K/Akt1/PKC zeta/Rac1/Cdc42 pathway in neurite outgrowth of postnatally born SVZ neurons.