The goal of this project is to establish the role of estrogen receptors (ERs) as regulators of neural progenitor cells (NPCs) in the developing cerebellum. Sex steroid hormones are known to influence both the proliferation of NPCs and the survival and maturation of neurons, but the role of ERs in this context has not been well studied. While ERs have been found to be important for certain brain functions, the lack of a suitable knock-out mouse model and difficulties in obtaining pure populations of NPCs have left the role of ERs in the cerebellum an open question. The proposal describes a powerful transgenic tool we have recently developed for purifying and characterizing cerebellar neural progenitors in the adult and immature mice. We now propose to characterize the cerebellar ER system in the adult mice and at different developmental stages in order to better understand its function in this area of the brain. The cerebellar ER protein distribution, its interactions with other proteins and possible colocalization with specific sets of ER binding sites will be determined with immunocytochemical, biochemical and genetic approaches. ERs will be ablated selectively in cerebellar NPCs and their progeny with the use of a conditional knock-out mouse line developed recently in this laboratory. Abnormalities in the cerebellar neuron population in the ER knock-out mouse will then be determined. These studies should help us better understand the specific functions that ERs regulate in NPCs and neurogenesis in the developing brain. [unreadable] [unreadable] [unreadable]