Many vertebrate and invertebrate organisms, including humans, retain the ability to make new neurons throughout life and to incorporate these into circuits in the adult brain. This process of adult neurogenesis occurs in the crayfish brain via a system that has many features in common with higher vertebrates, suggesting a common strategy for the generation of new neurons in adult brains. However, neuronal precursor cells in the crayfish brain are spatially separated, allowing studies on specific components of the lineage. This organization and other aspects of the crayfish system provide unique opportunities to explore the sequence of cellular and molecular events leading to the production of adult-born neurons. In the crayfish brain, first-generation precursors (neuronal stem cells) are not self-renewing, but instead are replenished from a source external to their niche. In vitro experiments suggest the hematopoietic (blood-producing) system as one source of these cells. This proposal will, (1) explore the structure and functional regulation of the first-generation neuronal precursor cells; (2) examine the influence of endogenous and environmental agents on the precursor lineage; and (3) probe the attraction mechanisms between blood cells and the niche in real time with time-lapse cell tracking. If a relationship between blood cells and neuronal stem cells is confirmed by these studies, it is anticipated that this project will have profound implications on our understanding of the mechanisms responsible for the development and evolution of the nervous system. The primary impact of these studies will be to define further the origins and function of neuronal stem cells, to promote a re-examination of the relationship between the hematopoietic and nervous systems in an evolutionary context, and to train numerous undergraduate students as the next generation of young neuroscientists.