Angiopoietin-2 Regulates Cortical Neurogenesis in the Developing Telencephalon

Abstract

Vascular-specific growth factor angiopoietin-2 (Ang2) is mainly involved during vascular network setup. Recently, Ang2 was suggested to play a role in adult neurogenesis, affecting migration and differentiation of adult neuroblasts in vitro. However, to date, no data have reported an effect of Ang2 on neurogenesis during embryonic development. As we detected Ang2 expression in the developing cerebral cortex at embryonic day E14.5 and E16.5, we used in utero electroporation to knock down Ang2 expression in neuronal progenitors located in the cortical ventricular zone (VZ) to examine the role of Ang2 in cortical embryonic neurogenesis. Using this strategy, we showed that radial migration from the VZ toward the cortical plate of Ang2-knocked down neurons is altered as well as their morphology. In parallel, we observed a perturbation of intermediate progenitor population and the surrounding vasculature. Taken together, our results show for the first time that, in addition to its role during brain vasculature setup, Ang2 is also involved in embryonic cortical neurogenesis and especially in the radial migration of projection neurons.