Cortical neurogenesis

Key members involved in this project

• Dr Fernando Garcia Moreno
• Dr Navneet Vasistha

Understanding of cortical progenitor populations has widespread implications for stem cell biology, cortical neurogenesis, evolutionary biology and comparative biology—leading toward the 'holy grail' that is the comprehension of the expansion of the mammalian cerebral cortex.

Neurons in the neocortex originate in the ventricular zone (VZ), a pseudostratified proliferative epithelium containing multipotent neural stem cells located at the deep ventricular surface of the telencephalic wall. This proliferative compartment expresses various transcriptional factors (including Otx1, Tbr1 and Er81). Excitatory neocortical neurons are produced in the VZ of the dorsal pallium arising from asymmetric divisions of the radial glia progenitors. These migrate largely following the radial glia processes. In the VZ of the cortical neuroepithelium, radial glia first produce excitatory neurons, many of which migrate radially to make up the embryonic preplate and the deepest cortical layers of the adult. Later in development, divisions of radial glia produce cells called intermediate progenitors that detach from the ventricular surface and aggregate in a zone overlying the VZ, the subventricular zone (SVZ). The SVZ serves as an additional proliferative compartment and is under the control of the transcription factor Pax6 and expresses Svet1 and Tbr2. In the SVZ, cells undergo one to three more cell divisions and then migrate to make up the neocortex. Although this basic pattern in development is similar in all mammalian cerebral cortices and may occur in all vertebrates, the proportions and compartmentalisation of the various progenitors can be very different. We are interested in performing clonal analysis to reveal the the lineage relationships during cortical development.

Recently, several transcription factors, including Mash1, Ngn1/2, Pax6, Emx1/2, Er81, Otx1, Fezl and Tbr1/2 have emerged as important players in cell fate specification in rodents. The combinatorial expressions of these factors determine the different cortical cell fates and set up the basic coordinates for cortical arealization and basic connectivity. We study developmental gene expression patterns that will allow us to identify molecularly distinct progenitor domains in the telencephalon and to elucidate genetic interactions underlying the generation of unique cellular phenotypes and regionalization of the cerebral cortex.