Molecular and cellular regulation of olfactory neurogenesis during development and regeneration.

摘要

The olfactory epithelium (OE) undergoes continual neurogenesis and can fully regenerate after extensive injury. The regulation and cell dynamics of OE neural stem cells and progenitors is fundamental to our understanding of OE development and maintenance. In this thesis, I developed genetic tools to isolate specific neuronal progenitors in the OE to study their lineage capacity and molecular characteristics. Our data define the roles of two important bHLH transcription factors in ORN neurogenesis and provide insight into their molecular contribution to OE development. In parallel, using fate-mapping strategy and various OE regeneration paradigms, I demonstrate that horizontal basal cells (HBCs) in the OE function as adult neural stem cells. Our data show that HBCs serve as a reservoir of long-lived progenitors that remain quiescent under normal olfactory receptor neuron (ORN) turnover or even after acute, selective loss of mature ORNs. Under these conditions, neuronal progenitors in the globose basal cell (GBC) population are sufficient to replenish the neuronal loss. However, after extensive lesions, HBCs regenerate GBCs and subsequently repopulate both neuronal and non-neuronal OE lineages of the epithelium. These data support the notion that HBCs function as OE stem cells and demonstrate a new model of adult neurogenesis in which distinct cell populations contribute to normal neuronal turnover or upon traumatic injury.