Department of Physiology, Medical School, University of Patras, Greece
The adult neural stem cells (aNSCs) pool is located at the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subependymal zone (SEZ) in the wall of the lateral ventricle. The subependymal zone, consists of NSCs, with self-renewing and differentiating ability and the postmitotic multiciliated ependymal cells, an important structural and trophic component of the niche. The niche is established at postnatal stages from a subpopulation of radial glial cells, determined during embryogenesis.
A small subpopulation of radial glial cells contributes to the generation of adult NSCs and multiciliated ependymal cells, which reside in the subventricular zone at lateral walls of the adult cortex. Towards understanding the mechanisms that control RGs fate decisions, we have identified two novel proteins Idas (MCIDAS) and Gemc1/Lynkeas, sharing homology with Geminin.
Our analysis showed that radial glial cells upon Idas or Lynkeas overexpression lose their characteristics and prematurely differentiated into multiciliated ependymal cells, while inactivation experiments resulted in blockage of multiciliated ependymal cells generation and promotes hydrocephalus. We have also shown that Idas and Lynkeas, in collaboration with E2F5, regulate the expression of known transcription factors essential for the commitment and differentiation of radial glial cells towards ependymal cells. We have also shown that Idas and Lynkeas act upstream of known transcription factors essential for the commitment and differentiation of RGs towards ependymal cells, while they are negatively regulated by Notch pathway. Our results show that Idas and Lynkeas are key players for radial glial cells fate commitment.