Advanced Medical Scientist-Programm 2019

Thema: "Deciphering the developmenal origin and aging mechanisms of adult hippocampal neural stem cells through manipulation of cyclin D2"

Zusammenfassung:
Hippocampal neurogenesis is one of the most unique phenomena in the adult brain, as it continuously provides new neurons that confer an extraordinary degree of plasticity to the hippocampal circuitry, which is important for learning and memory. Perturbations of this process have been linked to neurological disorders and cognitive aging. Understanding how the generation of neurons from neural stem cells (NSCs) is controlled during development and aging is crucial to harness their therapeutic potential in regenerative medicine. Our previous studies suggest that cyclin D2 (D2) is critical for adult neurogenesis and for the establishment of the adult NSC population during postnatal development. In order to evaluate these findings with more precision, we have generated transgenic mice that allow the spatiotemporally controlled conditional deletion of D2. By using these mice in combination with in vivo lineage tracing and next generation sequencing, this project aims at validating the role of cyclin D2 for self-renewal and maintenance of the adult NSCs pool and to identify critical mechanisms of NSC aging. By extending these analyses to the postnatal period, this project further aims to elucidate the origin and the dynamic development of adult hippocampal NSC populations, which defines the initial amount of available NSCs and therefore the neurogenic potential throughout life.