Distinct Embryonic Origin for Postnatal Dentate Neural Stem Cells

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): The discovery of neural stem/progenitor cells and persistent neurogenesis in restricted brain regions has ignited an unprecedented interest in developing cell restoration therapies, which are designed to repair the malfunctional cells and/or replace the defunct cells in the nervous system in the case of diseases or injuries. Conceivably, we can achieve these either by coaching endogenous stem/progenitor cells for self-repair/self-replenishment, or by transplanting exogenous stem/progenitor cells to differentiate in a defined manner to restore defective or lost cells. However, the successful utilization of neural stem/progenitor cells in either case is contingent on their ability to behave and function in vivo n a biologically meaningful way without causing adverse effects. Many studies in recent years indicate that the fate and behavior of stem/progenitor cells are governed by the local microenvironment, termed the "niche". Therefore, a better understanding of the interactions between the stem/progenitor cells and their niche is a critical step toward effective stem cell therapies. We hope to elucidate the molecular cues mediating interactions between stem/progenitor cells and their niche during development and to encourage use of this knowledge to develop novel approaches for treating neural injuries and neurodegenerative diseases through the following two aims. Aim #1: Examine the contribution of the ventral hippocampal ventricular zone to the production of subgranular NSCs throughout the hippocampus. Aim #2: Characterize the roles of various sources of Shh in SGZ development.