Achieving tissue homeostasis in the adult organism requires the continual replacement of cells which have died due to aging, damage or disease. While it was once thought that the adult brain was an exception to this aspect of tissue regulation, it is now known that the brain contains several regions where neurogenesis occurs throughout life. This laboratory recently described a series of new sites in the brain, found in the adult circumventricular organs (CVOs), that contains cells expressing stem cell-like traits. Traditionally, CVOs have been referred to as the "windows of the brain" because of their unique ability to sense physiological stimuli in blood and secrete factors into cerebrospinal fluid. These properties of the CVOs, and their cells with stem cell-like properties, raise the intriguing hypothesis that CVOs represent novel niches for cell genesis important for homeostasis in the adult brain. This project is designed to characterize further the putative stem cells residing in the CVOs of mice. The PI's laboratory has generated genetically engineered CVO stem cells that are tagged and can be tracked allowing their survival, migration and differerentiation to be followed in the adult brain. In addition, this project will explore whether the fate of tagged CVO stem cells can be re-directed following their transplantation to distinct CVO niches. The overall goal of these studies is the discovery and characterization of new sites for cell genesis in the adult brain that are important for maintaining brain homeostasis in response to changing physiological, environmental, and/or pathological stimuli. Moreover, by training both undergraduate and graduate students, this project will foster the development of the next generation of scientists in stem cell biology, an important new area of scientific inquiry.