Elucidation of the mechanisms determining neural stem cells fate and identification of the niche in the adult SVZ and hippocampus

• Applicant: Professor Dr. Verdon Taylor, Ph.D.
• Subject Area: Developmental Neurobiology
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 28996474

The aims of this project are, to determine the identity of adult neural stem cells (NSCs) in the neurogenic regions of the postnatal mouse brain, to elucidate the niche that regulates their development and differentiation and to establish the molecular mechanisms that control neurogenesis in these brain regions. We have recently shown that Jagged1/Notch1 signaling is pivotal for NSC maintenance. Thus, we believe that Notch1 signaling is a marker of NSCs in the adult brain. In order to monitor Notch activity in vivo, we have generated transgenic mice (Hes5-GFP) that express green fluorescent protein from regulatory elements of the neural specific, Notch target gene Hes5 (see section 2.2 Preliminary work). We hypothesize that the cells in the neurogenic regions of the adult brain that display active Notch signaling are NSCs. We will determine the antigenic characteristics, cell-cycle kinetics and stem cell potential of Hes5-GFP expressing cells of the adult brain in vivo and ex vivo. In the two related projects, we will use SVZ and hippocampal slice cultures to monitor the behavior of individual Hes5-GFP positive cells. In addition, we will sort Hes5-GFP positive cells from defined regions of the postnatal brain, assess their growth factor responses and their potential in vitro, and capacity in vivo by transplantation.

• DFG Programme: Research Grants