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(申请人提供)：中枢神经系统退行性变导致多种病理情况。这些疾病包括阿尔茨海默氏症和帕金森氏症等神经退行性疾病，以及胶质瘤和少突胶质瘤等肿瘤病理。在这种背景下，人们对内源性神经前体细胞修复或替换受损神经组织的潜力越来越感兴趣。最近，我们观察到，虽然Id2-/-小鼠的大脑似乎发育正常，但成年人的嗅球较小。我们推测，虽然Id2对于大脑发育来说似乎是可有可无的，但它可能在成人神经发生中具有重要的发育后作用。我们的初步数据显示，Id2基因缺失小鼠嗅球的形态缺陷与成年神经前体细胞来源的神经发生减少一致。此外，我们还观察到Id2缺失的神经前体细胞在体外表现出明显的自我更新丧失和神经分化早的表型。在这项建议中，我们概述了一系列实验，以更好地了解Id2在维持成年神经前体细胞库中的分子机制。在这里，我们建议采用体内和体外研究，以监测Id2缺失神经前体细胞自我更新的能力和对成年神经发生的特异性贡献。此外，我们建议通过研究Id2通过直接上游抑制神经原来阻断NeuroD1的神经发生活性，从分子水平上剖析Id2在维持神经发生中的作用。这项研究提案代表了一种新的分析，旨在建立Id2在成人神经发生中的特定作用，与其他ID基因不同。随着发育，成年大脑中维持着一群多潜能的神经前体细胞。这些细胞有助于嗅觉，对缺血损伤做出反应，并被认为与癌症有关。这一建议旨在研究Id2在维持祖细胞库的可塑性中的作用。这些实验与这些独特细胞的治疗潜力的实现直接相关。

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