FBS Colloquia No.290Cellular and Molecular Neurobiology Group

What is the role of indirect neurogenesis in the formation of the cerebral cortex?

Cortical excitatory neurons originate from radial glial cells (RGCs) in the cortical ventricular zone. RGCs initially undergo symmetric cell division to amplify progenitors, but once they enter the neurogenic stage, they undergo asymmetric cell division to produce a progenitor and a neuron (direct neurogenesis), or a progenitor and an intermediate neuronal progenitor, which further divides to produce neurons (indirect neurogenesis). Although these processes have been revealed by imaging techniques in vitro, their contribution to the cortical formation in vivo remains obscured. To address this issue, we developed two genetically labeling methods, one identifies neurons derived from indirect neurogenesis, and the other identifies sister neurons derived from an INP in vivo. First, we used a mouse G2A line that expresses CreERT2 under the control of the putative neurogenin2 promoter. We crossed the G2A line with Ai14 mice (ROSA26-lsl-tdTomato) and administered a limited amount of tamoxifen to G2A:Ai14 pregnant mice. Since CreERT2 is expressed in cells committed to neurons, a combination of tamoxifen with sequential EdU administrations allowed us to identify neurons derived from direct (tdTomato+/EdU-) and indirect neurogenesis (tdTomato+/EdU+) at a given point in time. Our preliminary results suggest a difference in the contribution of direct and indirect neurogenesis between the early and later stages of cortical formation. Second, we crossed the G2A line with the mouse line for Mosaic Analysis with Double Markers (MADMs) to label mitotic cells of Ngn2-lineage. The results suggest that indirect neurogenesis mostly produces a pair of neurons that shares similar neuronal phenotypes. Although our research is still underway, we would like to introduce recent progress and discuss the role of indirect neurogenesis in cortical formation.