Control of Cell Proliferation and Differentiation in the Developing Retina

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并不清楚。 知道的这项资助的目的是研究发育信号通路的机制， 与细胞内转录因子相互作用，控制细胞生长、增殖和分化， 果蝇发育中的视网膜果蝇发育中的视网膜非常适合于所提出的 研究，因为细胞生长，增殖和分化的良好特征区域， 与不同信号传导途径和细胞内转录的良好特征区域相结合， 这些因素，以及果蝇系统中可用的大量工具。 Notch信号通路是一种保守的发育信号通路，在眼内发育过程中发挥着不同的作用 在细胞发育过程中，细胞增殖、分化和细胞命运的决定。有趣的是， 在发育中的视网膜的不同区域中Notch信号传导的激活导致不同的结果： 信号传导诱导发育中的视网膜前部的细胞生长和增殖， 在形态发生沟之前的细胞中的分化。我们假设， Notch信号传导诱导其靶标在发育中的视网膜的不同区域中的表达， 受Notch和其他信号通路或区域特异性因子之间的相互作用控制， 不同靶点的表达介导了Notch信号在诱导细胞凋亡中的不同作用。 在发育中的视网膜的不同区域中的增殖或分化。为了验证这些假设， 阐明细胞增殖和分化在发育中的视网膜中被控制的机制， 我们有以下三个具体的目的：（1）研究Notch 信号调节发育中视网膜的细胞周期;（2）研究细胞周期调控的机制， Notch信号传导促进细胞生长和增殖的能力受到控制;（3）为了表征Notch信号传导， 在果蝇发育中的视网膜中控制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，这将可能导致新的预防方法的发展， 诊断和治疗视网膜疾病以及其他具有细胞增殖的人类疾病， 分化缺陷

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.