Notobranchius furzeri: New types of neuronal stem cells – new insights in neuro(re)genesis

The adult mammalian brain possesses two neurogenic niches of which the neurogenic potential declines steeply with age. Yet teleost fish, possess sixteen neurogenic niches and exhibit a very high potential for adult neurogenesis. Most remarkably, they can regenerate tissue, including brain, upon injury. The African turquoise killifish recently gained much attention as potent ageing model based on its short life cycle, explosive growth and the finding of peculiar and abundant highly-proliferative neuronal progenitor cells (hpNPCs) in its telencephalon, next to the commonly recognized radial glia type NPCs as in zebrafish. The exact genotype-phenotype of these hpNPCs and possibly other killifish NPC types remains elusive. Their involvement in neuro-re-generation in the (injured) (aged) brain is the topic of this project, targeted at finding new therapies to adapt the non-permissive environment of the aged mammalian brain to combat neurodegenerative disease. We will completely characterise the different stem cell populations at transcriptome and proteome level in the killifish telencephalon. We will define their phenotype in neurogenesis in the young and aged brain. We aim at restoring the decline in neurogenesis via knockout of NPC-specific genes/proteins identified in the differential genetic/proteomic screen. We will study the function of the different NPC populations during neuroregeneration upon injury in young and aged brain.