Tight regulation of neural stem cell (NSC) maintenance and differentiation is crucial for the formation of the central nervous system and homeostatic neurogenesis in adults.
In the adult brain, neurogenesis ceases at most locations in the brain and remains active only into two distinct neurogenic niches: a. the ventricular-subventricular zone (V-SVZ) of the lateral ventricle walls and b. the subgranular zone of the hippocampal dentate gyrus (DG). Notch signalling has been implicated in modulation of neurogenesis in both V-SVZ and hippocampal DG, with multiple Notch receptors being expressed in these NSC niches.
Previous work from our group has shown that Notch1 and Notch2 proteins are co-expressed in NSC populations of the adult neurogenic niches, albeit playing distinct roles in adult neurogenesis. Specifically, Notch1 protein regulates adult neurogenesis primarily at the level of activated NSCs, and genetic deletion of Notch1 selectively depletes the active NSC pool, through differentiation and exhaustion of activated NSCs.
In contrast, genetic deletion of Notch2 results in activation of dormant NSCs, expansion of the active NSC pool and increases neurogenesis. Hitherto, the differential mechanism of function between Notch1 and Notch2 proteins in adult neurogenesis remains elusive. Via generating mouse models for in vivoprotein tagging and using ChIP-Sequencing and Mass Spectrometry approaches, we are aiming to elucidate how Notch1 and Notch2 proteins specifically control different aspects of adult neurogenesis.