Distinct Embryonic Origin for Postnatal Dentate Neural Stem Cells

描述（由申请人提供）：神经干细胞/祖细胞和局限性脑区域中的持续神经发生的发现激发了对开发细胞恢复疗法的前所未有的兴趣，这些疗法旨在修复神经系统中的功能障碍细胞和/或在疾病或损伤的情况下替换神经系统中的失效细胞。可以想象，我们可以通过训练内源性干/祖细胞进行自我修复/自我补充，或者通过移植外源性干/祖细胞以确定的方式分化以恢复缺陷或丢失的细胞来实现这些。然而，神经干/祖细胞在任一情况下的成功利用取决于它们在体内以生物学上有意义的方式表现和发挥功能而不引起不良反应的能力。近年来许多研究表明，干/祖细胞的命运和行为受局部微环境（称为“生态位”）的控制。因此，更好地了解干/祖细胞及其生态位之间的相互作用是有效干细胞治疗的关键一步。我们希望阐明介导干/祖细胞和他们的小生境在发展过程中的相互作用的分子线索，并鼓励利用这些知识，通过以下两个目标，开发新的方法来治疗神经损伤和神经退行性疾病。目的#1：检查腹侧海马脑室区对整个海马产生颗粒下NSC的贡献。目标#2：描述SGZ发展中Shh的各种来源的作用。

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.