The In Vivo Function of Id2 in Retinal Proliferation and Differentiation

Id2在视网膜增殖和分化中的体内功能

• 批准号: 7673715
• 负责人: Rosa A Uribe
• 金额: $ 3.44万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673715
• 关键词: Affect; Cancerous; Cell Count; Cell Culture Techniques; Cell Cycle; Cell Cycle Progression; Cell Line; Cell Proliferation Regulation; Cell Survival; Cell division; Cells; Commit; Defect; Development; Developmental Process; Diagnostic Neoplasm Staging; Differentiation and Growth; Disease; Embryonic Eye; Event; Exhibits; Eye; Family; Fertilization; Goals; Growth; Helix-Turn-Helix Motifs; Human; Intrinsic factor; Knowledge; Learning; Light; Link; Location; Malignant Neoplasms; Mediating; Mediator of activation protein; Methods; Microphthalmos; Molecular; Nature; Nervous system structure; Neurodegenerative Disorders; Neurologic; Neuronal Differentiation; Neurons; Pathway interactions; Pattern; Phase; Play; Process; Property; Protein Family; Proteins; Regulation; Regulatory Pathway; Retina; Retinal; Retinoblastoma; Role; Series; Signal Pathway; Signal Transduction; Sonic Hedgehog Pathway; Testing; Time; Tissues; Undifferentiated; Zebrafish; blastomere structure; gain of function; human disease; in vivo; loss of function; nerve stem cell; neuroblast; neurogenesis; novel; relating to nervous system; research study; retinal neuron; retinal progenitor cell; retinogenesis; segregation; smoothened signaling pathway; Affect; Cancerous; Cell Count; Cell Culture Techniques; Cell Cycle; Cell Cycle Progression; Cell Line; Cell Proliferation Regulation; Cell Survival; Cell division; Cells; Commit; Defect; Development; Developmental Process; Diagnostic Neoplasm Staging; Differentiation and Growth; Disease; Embryonic Eye; Event; Exhibits; Eye; Family; Fertilization; Goals; Growth; Helix-Turn-Helix Motifs; Human; Intrinsic factor; Knowledge; Learning; Light; Link; Location; Malignant Neoplasms; Mediating; Mediator of activation protein; Methods; Microphthalmos; Molecular; Nature; Nervous system structure; Neurodegenerative Disorders; Neurologic; Neuronal Differentiation; Neurons; Pathway interactions; Pattern; Phase; Play; Process; Property; Protein Family; Proteins; Regulation; Regulatory Pathway; Retina; Retinal; Retinoblastoma; Role; Series; Signal Pathway; Signal Transduction; Sonic Hedgehog Pathway; Testing; Time; Tissues; Undifferentiated; Zebrafish; blastomere structure; gain of function; human disease; in vivo; loss of function; nerve stem cell; neuroblast; neurogenesis; novel; relating to nervous system; research study; retinal neuron; retinal progenitor cell; retinogenesis; segregation; smoothened signaling pathway

DESCRIPTION (provided by applicant): The construction of the nervous system is an integrated series of developmental steps, commencing with the segregation of a small group of embryonic cells fated to become neural progenitors. These neural progenitors then remain proliferative and undifferentiated until they have become committed to distinct neural cell fate. As in most neural tissue, within the vertebrate retina, the cell and molecular strategies that cells use to control these processes remain poorly understood. Even worse, most forms of cancer exhibit distinctly misregulated control over these events, and the nature underlying many human diseases are tied to perturbations in these processes. Therefore, the overarching goal of this proposal is to enhance our understanding of the intracellular mechanisms governing neuroblast proliferation, lineage commitment and differentiation within the developing vertebrate retina. This will be accomplished by utilizing the zebrafish retina to understand the role of the intrinsic factor Id2 (Inhiibitor of Differentiation) in retinal development. The specific Aims of this proposal are 1. To determine the function of Id2 during zebrafish retinogenesis, 2. To determine the molecular mechanisms underlying Id2 function in the developing zebrafish retina, and 3. To determine if Id2 is regulated by the Sonic Hedgehog Pathway (Shh). These Aims will be accomplished using Id2 loss and gain-of-function strategies in vivo in order to define the functional role of Id2 during zebrafish retinogenesis, and Shh loss and gain-of-function methods will also be used to assess if Id2 is regulated by Shh in the developing vertebrate retina. The experiments in this proposal will shed light on how the intrinsic factor Id2 regulates growth and differentiation of the vertebrate eye, and how it's function may be controlled by mitogenic properties of the Shh signaling pathway. As the formation of many human neurological, developmental and cancerous diseases are linked to disruptions in such early developmental processes as cell division, cell specialization and cell survival, the purpose of this study is to enhance our understanding of how these processes normally occur at the molecular level within the cell, and how they are controlled over developmental time. Specifically, this study will examine how these events occur in the developing retina, thereby increasing our knowledge of how the retina forms, and providing clues to the events that may be disrupted in the early stages of cancer, such as retinoblastoma, as well as neurodegenerative diseases affecting the retina.

描述（由申请人提供）：神经系统的构建是一系列综合的发育步骤，从隔离一小组胚胎细胞的隔离开始，以成为神经祖细胞。然后，这些神经祖细胞保持增殖和未分化，直到致力于独特的神经细胞命运。与大多数神经组织一样，在脊椎动物视网膜中，细胞用来控制这些过程的细胞和分子策略仍然知之甚少。更糟糕的是，大多数形式的癌症对这些事件表现出明显误导的控制，并且在这些过程中，许多人类疾病的性质与扰动有关。因此，该提案的总体目标是增强我们对发展脊椎动物视网膜内神经细胞增殖，谱系承诺和分化的细胞内机制的理解。这将通过利用斑马鱼视网膜来了解内在因子ID2（分化的Inhiibitor）在视网膜发育中的作用。该提案的具体目的是1。确定斑马鱼视网膜生成期间ID2的功能，2。确定发育中的斑马鱼视网膜中ID2功能的分子机制，以及3。确定ID2是否受Sonic HedgeHog途径（SHH）调节。这些目标将使用ID2损失和体内功能获得策略来实现，以定义斑马鱼视网膜生成过程中ID2的功能作用，而SHH损失和功能获得的方法也将用于评估ID2是否受SHH在发育中的静脉视网膜中的调节。该提案中的实验将阐明固有因子ID2如何调节脊椎动物眼的生长和分化，以及如何通过SHH信号通路的有丝分裂特性来控制其功能。由于许多人类神经，发育和癌性疾病的形成与在细胞分裂，细胞专业化和细胞存活等早期发育过程中的破坏有关，这项研究的目的是增强我们对这些过程通常在细胞内分子水平上如何发生以及如何控制发育时间的理解。具体而言，这项研究将研究这些事件如何发生在发展中的视网膜中，从而增加了我们对视网膜形成方式的了解，并为可能在癌症早期阶段被破坏的事件提供线索，例如视网膜母细胞瘤，以及影响视网膜的神经退行性疾病。