Control of Cell Proliferation and Differentiation in the Developing Retina

视网膜发育中细胞增殖和分化的控制

• 批准号: 7350199
• 负责人: WEI DU
• 金额: $ 25.21万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7350199
• 关键词: Affect; Anterior; Cell Cycle; Cell Cycle Regulation; Cell Differentiation process; Cell Proliferation; Cells; Complex; Cyclin E; Defect; Depth; Development; Diagnosis; Doctor of Philosophy; Drosophila genus; Enhancers; Eye; Eye Development; Genes; Goals; Grant; Intrinsic factor; Investigation; Lead; Mediating; Molecular; Neurons; Outcome; Pathway interactions; Photoreceptors; Prevention; Range; Regulation; Research; Retina; Retinal; Retinal Diseases; Role; Signal Pathway; Signal Transduction; System; Testing; To specify; ato protein; cell growth; human disease; inhibitor/antagonist; notch protein; novel strategies; tool; transcription factor

Cell proliferation and differentiation is coordinately regulated during normal retinal development. However, the molecular mechanisms by which cell proliferation and differentiate are controlled are not known. The goal of this grant is to investigate the mechanisms by which developmental signaling pathways and cell intrinsic transcription factors interact in the control of cell growth, proliferation and differentiationin the Drosophila developing retina. The Drosophila developing retina is ideally suited for the proposed research because of the well-characterized zones of cell growth, proliferation, and differentiation in conjunction with the well-characterized zones of different signaling pathways and cell intrinsictranscriptional factors, and because of the large set of tools that are available in the Drosophila system. Notch signaling is a conserved developmental signaling pathway that has diverse roles in eye development ranging from cell proliferation, differentiation, and cell fate determination. Interestingly, activation of Notch signaling in different regions of the developing retina leads to different outcomes: Notch signaling induces cell growth and proliferation in the anterior of the developing retina but induces differentiation in cells just ahead of the morphogenetic furrow. We hypothesize that the distinct ability of Notch signaling to induce the expression of its targets in different regions of the developing retina is controlled by the interactions between Notch and other signaling pathways or region specific factors, and that the expression of distinct set of targets mediates the different effect of Notch signaling in inducing cell proliferation or differentiation in different regions of the developing retina. To test these hypotheses and to elucidate the mechanisms by which cell proliferation and differentiation is controlled in the developing retina, we have the following three Specific Aims: (1) To investigate the molecular mechanisms by which Notch signaling regulates the cell cycle in the developing retina; (2) To investigate the mechanisms by which the ability of Notch signaling to promote cell growth and proliferation is controlled; (3) To characterize the mechanism by which the initiation of Ato expression is controlled in the Drosophila developing retina. Our long-term objective is to achieve a deep understanding of cell proliferation and differentiation in retinal development, which will potentially lead to the development of new approaches in the prevention, diagnosis, and treatment of retinal diseases as well as other human diseases with cell proliferation or differentiation defect.

在正常视网膜发育过程中，细胞增殖和分化受到协调调节。 然而，控制细胞增殖和分化的分子机制尚不清楚。 已知。这笔赠款的目的是研究发育信号通路的机制 和细胞内在转录因子相互作用，控制细胞生长、增殖和分化 果蝇视网膜正在发育。果蝇视网膜发育非常适合所提出的 研究是因为细胞生长、增殖和分化的区域具有明确的特征 与不同信号通路和细胞内在转录的明确特征区域相结合 因素，以及果蝇系统中可用的大量工具。 Notch信号是一种保守的发育信号通路，在眼睛中具有多种作用 发育范围包括细胞增殖、分化和细胞命运决定。有趣的是， 在发育中的视网膜的不同区域激活Notch信号会导致不同的结果：Notch 信号传导诱导发育中视网膜前部的细胞生长和增殖，但诱导 细胞在形态发生沟之前分化。我们假设独特的能力 Notch 信号在视网膜发育的不同区域诱导其靶标的表达 由Notch和其他信号通路或区域特定因素之间的相互作用控制，并且 不同靶标的表达介导诱导细胞中Notch信号传导的不同作用 发育中的视网膜不同区域的增殖或分化。为了检验这些假设并 阐明发育中的视网膜中控制细胞增殖和分化的机制， 我们有以下三个具体目标：（1）研究Notch的分子机制 信号传导调节视网膜发育中的细胞周期； (2) 探讨其机制 Notch信号传导促进细胞生长和增殖的能力受到控制； (3) 表征 果蝇视网膜发育中控制 Ato 表达起始的机制。 我们的长期目标是深入了解细胞增殖和分化 视网膜发育，这将有可能导致预防新方法的开发， 视网膜疾病以及其他与细胞增殖或相关的人类疾病的诊断和治疗 分化缺陷。