Molecular mechanisms underlying adult SVZ neurogenesis

DESCRIPTION (provided by applicant): Neural stem cells reside in the subventricular zone (SVZ) of adult mammals continuously producing multiples types of olfactory bulb (OB) interneurons. The generation of diverse types of neurons within the adult brain must be tightly regulated in order to maintain a functional circuit with high turnover of its neuronal components; however, the molecular mechanism underlying generation of such diversity is unknown. Our recent data shows that the transcription factor Pax6 is required for the generation of dopaminergic OB interneurons. The expression of another factor Er81 in a distinct pattern from Pax6 in the adult OB suggests that different transcriptional machineries may function in the production of OB interneuron subtypes. In this application, we aim to determine which OB interneuron subtype requires Er81. We also plan to analyze which embryonic progenitor zones can contribute to OB neurogenesis to gain insight into the molecular players of adult neuronal diversity. Thirdly, we aim to compare the molecular expression profiles of adult neural stem cells. Understanding the mechanism underlying neuronal diversity within the brain will be important for future therapies to replace damaged neurons in diseases and trauma.