The Role of Id2 in Adult Neurogenesis

描述（由申请人提供）：中枢神经系统变性导致多种病理状况。这些包括神经退行性疾病，包括阿尔茨海默氏症和帕金森氏症，以及肿瘤病理学，如神经胶质瘤和少突胶质细胞瘤。在这种情况下，越来越多的兴趣围绕内源性神经祖细胞修复或替代受损神经组织的潜力。最近，我们观察到，虽然Id 2-/-小鼠的大脑似乎发育正常，但成年小鼠的嗅球较小。我们推测，虽然Id 2似乎是大脑发育的关键，但它可能在成人神经发生中具有重要的发育后作用。我们的初步数据表明，形态缺陷的Id 2无效小鼠嗅球与成年神经祖细胞衍生的神经发生减少一致。此外，我们观察到，Id 2空神经祖细胞显示出惊人的表型，其特征在于失去自我更新和过早的神经分化在体外。在这个建议中，我们概述了一系列的实验，以更好地了解Id 2在维持成人神经祖细胞库的分子机制。在这里，我们建议采用在体内和体外研究，以监测Id 2空神经祖细胞自我更新的能力，并特别有助于成人神经发生。此外，我们建议解剖的Id 2在维持神经发生的分子水平上的作用，通过调查的能力，Id 2通过直接上游抑制Neurogenin阻断NeuroD 1的神经原性活动。这项研究提案代表了一种新的分析，旨在建立一个特定的作用，Id 2在成人神经发生，这是不同于其他Id基因。在发育之后，多能神经祖细胞群体维持在成人脑中。这些细胞有助于嗅觉，对缺血性损伤作出反应，并与癌症有关。该建议旨在研究Id 2在维持祖细胞库的可塑性中的作用。这些实验与实现这些独特细胞的治疗潜力直接相关。

DESCRIPTION (provided by applicant): Multiple pathological conditions result from degeneration of the central nervous system. These include neurodegenerative diseases including Alzheimer's and Parkinson's, as well as neoplastic pathologies such as glioma and oligodendrogioma. In this context increasing interest surrounds the potential of endogenous neural progenitor cells to repair or replace damaged neural tissue. Recently, we have observed that while the brains of Id2 -/- mice appear to develop normally, adults have smaller olfactory bulbs. We hypothesize that while Id2 appears dispensable for brain development, it may have an important post-developmental role in adult neurogenesis. Our preliminary data demonstrate morphological defects in the olfactory bulbs of Id2 null mice consistent with a decrease in adult neural progenitor derived neurogenesis. In addition, we observe that Id2 null neural progenitor cells display a striking phenotype characterized by loss of self-renewal and premature neural differentiation in vitro. In this proposal, we outline a series of experiments to better understand the molecular mechanisms of Id2 in maintenance of the adult neural progenitor pool. Here we propose to employ both in vivo and in vitro studies in order to monitor the ability of Id2 null neural progenitors to self-renew and contribute specifically to adult neurogenesis. Further, we propose to dissect the role of Id2 in maintenance of the neurogenesis on a molecular level by investigating the ability of Id2 to block the neurogenic activities of NeuroD1 via direct upstream inhibition of Neurogenin. This research proposal represents a novel analysis that is designed to establish a specific role for Id2 in adult neurogenesis that is distinct from other Id genes. Following development, a population of multi-potent neural progenitor cells is maintained in the adult brain. These cells contribute to olfaction, respond to ischemic injury and are putatively linked to cancer. This proposal is designed to investigate the role of Id2 in maintaining the plasticity of the progenitor cell pool. These experiments are immediately relevant to realization of the therapeutic potential of these unique cells.