The Role of Id2 in Adult Neurogenesis

Id2 在成人神经发生中的作用

• 批准号: 7407036
• 负责人: Matthew Charles Havrda
• 金额: $ 4.68万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7407036
• 关键词: Adult; Alzheimer' s Disease; Binding; Brain; CNS degeneration; Cells; Condition; Data; Defect; Development; Employee Strikes; Genes; Glioma; In Vitro; Injury; Knockout Mice; Link; Maintenance; Malignant Neoplasms; Molecular; Monitor; Mus; Neurodegenerative Disorders; Neurons; Parkinson Disease; Pathology; Pathway interactions; Phenotype; Population; Production; Research Proposals; Role; Series; Smell Perception; Stem cells; Stream; Testing; Therapeutic; Tissues; design; in vivo; interest; neoplastic; nerve stem cell; neurogenesis; novel; olfactory bulb; progenitor; relating to nervous system; repaired; research study; self-renewal

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.

描述（由申请人提供）：多种病理状况是由中枢神经系统退化引起的。其中包括包括阿尔茨海默氏症和帕金森氏症在内的神经退行性疾病，以及神经胶质瘤和寡糖瘤等肿瘤病理学。在这种情况下，人们增加了兴趣，围绕着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，尽管ID2 - / - 小鼠的大脑似乎正常发育，但成年人的嗅球较小。我们假设，尽管ID2似乎可以用于大脑发育，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，与成年神经祖细胞衍生的神经发生的降低一致的ID2无效小鼠的嗅球形态缺陷。此外，我们观察到ID2无效神经祖细胞显示出惊人的表型，其特征是体外自我更新和早产神经分化。在此提案中，我们概述了一系列实验，以更好地了解ID2在维持成人神经祖细胞库中的分子机制。在这里，我们建议使用体内和体外研究，以监测ID2无效神经祖细胞自我更新并专门为成人神经发生做出贡献的能力。此外，我们建议通过研究ID2通过直接上游抑制神经蛋白来阻止神经元的神经源性活性的能力，从而阐明ID2在分子水平维持神经发生中的作用。该研究建议代表了一种新的分析，该分析旨在在成人神经发生中确立ID2的特定作用，该作用与其他ID基因不同。发展后，成人大脑中维持了多功能神经祖细胞的种群。这些细胞有助于嗅觉，对缺血性损伤做出反应，并与癌症相关。该建议旨在研究ID2在维持祖细胞池的可塑性中的作用。这些实验与实现这些独特细胞的治疗潜力有关。

项目成果

Id2 is required for specification of dopaminergic neurons during adult olfactory neurogenesis.

• DOI: 10.1523/jneurosci.3188-08.2008
• 发表时间: 2008-12-24
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Havrda MC;Harris BT;Mantani A;Ward NM;Paolella BR;Cuzon VC;Yeh HH;Israel MA
• 通讯作者: Israel MA