Distinct Embryonic Origin for Postnatal Dentate Neural Stem Cells

描述(申请人提供)：神经干细胞/祖细胞和在受限的脑区持续神经发生的发现点燃了人们对开发细胞修复疗法的前所未有的兴趣，这种疗法旨在修复神经系统中的功能失调的细胞和/或在疾病或损伤的情况下替换神经系统中不存在的细胞。可以想象，我们可以通过指导内源性干细胞/祖细胞进行自我修复/自我补充，或者通过移植外源性干细胞/祖细胞以特定的方式分化来修复有缺陷或丢失的细胞来实现这一点。然而，在任何一种情况下，神经干细胞/祖细胞的成功利用都取决于它们在体内以一种具有生物学意义的方式表现和发挥作用的能力，而不会造成不良影响。近年来的许多研究表明，干细胞/祖细胞的命运和行为受局部微环境的支配，这种微环境被称为“生态位”。因此，更好地了解干细胞/祖细胞及其利基之间的相互作用是迈向有效干细胞疗法的关键一步。我们希望阐明在发育过程中调节干细胞/祖细胞及其生态位之间相互作用的分子线索，并鼓励利用这一知识通过以下两个目标开发治疗神经损伤和神经退行性疾病的新方法。目的#1：研究海马室腹区在整个海马区颗粒下神经干细胞产生中的作用。目的#2：描述不同来源的Shh在SGZ发育中的作用。

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.