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Open Access Highly Accessed Research article

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

Konstantin Khodosevich and Hannah Monyer

Author Affiliations

Department of Clinical Neurobiology, Interdisciplinary Center for Neuroscience, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany

BMC Neuroscience 2010, 11:18  doi:10.1186/1471-2202-11-18

Published: 10 February 2010

Abstract

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, PKCζ 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 PKCζ increased neurite length. PI3K, Akt1 and PKCζ 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/PKCζ/Rac1/Cdc42 pathway in neurite outgrowth of postnatally born SVZ neurons.