Determining mechanisms behind intermediate progenitors (IPs) formation in the developing cortex.

• Applicant: Dr. Froylan Calderon de Anda
• Subject Area: Developmental Neurobiology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 392669675

There are several types of neuronal progenitors in the developing cortex: 1) the radial glia, is known as structural element that constitutes the ventricular zone (VZ) and gives rise to neurons and glia during cortex development. Radial glia divides at apical (ventricular) surface and behaves as a self-renewal compartment: divides symmetrically or asymmetrically and maintained as progenitors pool in developing cortex. 2) The radial glia-like (RG) cells, self-renew, produce neuronal progenitors and neurons but lack contact with the ventricular zone. 3) Intermediate progenitors (IPs) or basal progenitors are generated from asymmetric divisions of radial glia. IPs predominantly undergo symmetrical division in subventricular zone/intermediate zone (SVZ/IZ), and generate only neurons. Thus, IPs are transiently amplifying progenitors that expand neuronal cell population. Despite the relevance of IPs in the developing cortex, the molecular mechanisms that regulate proliferation and differentiation of these cells are largely unknown. With the current proposal, we are testing the exciting hypothesis that Ca+2 influx might be a mechanism governing IPs formation in the developing cortex. Our preliminary results not only demonstrate that developing neurons attain a post-mitotic state gradually with a limited proliferative potential during this gradual process, but also show that developing neurons in the CP challenged with calcium influx re-express the IPs marker Tbr2. Therefore, we believe it is important to study the underlying mechanisms of how calcium signaling might lead to Tbr2 expression and thus IPs specification in the SVZ/IZ. We are encouraged by the success of our preliminary studies, and are seeking funding from DFG to further develop this project.

• DFG Programme: Research Grants
• Co-Investigator: Durga Praveen Meka, Ph.D.