Regulation of Eye Morphogenesis

眼睛形态发生的调节

• 批准号: 6784232
• 负责人: FRANK LASKI
• 金额: $ 37.41万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6784232
• 关键词: Drosophilidae; actins; cytogenetics; cytoskeleton; developmental genetics; eye; gel electrophoresis; gene expression; gene induction /repression; gene interaction; gene mutation; genetic mapping; green fluorescent proteins; histogenesis; polymerization; protein protein interaction; protein structure function; regulatory gene; transmission electron microscopy

DESCRIPTION (provided by applicant): To understand morphogenesis, one must know how the actin cytoskeleton forms and how it is taken apart. Presently there is little known about how this occurs in a developing animal and less still in a developing eye. Our goal is to bring light to this area of eye research, increasing our ability to visualize how the actin cytoskeleton is regulated during the morphogenesis of the eye. We will take a genetic approach, using Drosophila meIanogaster as a model system. We have been studying the twinstar (tsr) gene, which is the Drosophila homologue of cofilin, a protein which has a major role in reorganizing the actin cytoskeleton. We have shown that tsr is required for cell motility during ovary development. We have also been able to show that tsr is required during the morphogenesis of the retina by using a genetic technique that we developed called repressor sensitive (RS) mutation. With a tsr RS mutation, we can specifically repress the expression of tsr during late stages of eye development, allowing us to study the role of tsr at this stage without concern for tsr's affects in other tissues or other times of development. Our results suggest that tsr is required for the proper development of the rhabdomere and also for retinal elongation. We now propose to continue the analysis of the role of tsr during eye morphogenesis, and use the RS mutation technique to study the role of other actin cytoskeleton regulatory genes during eye morphogenesis, including the Drosophila homologues of LIM kinase, actin interacting protein 1 (Aip 1), PAK, rac and the Arp2/3 complex. We will also screen for novel genes that genetically interact with tsr during late stages of eye morphogenesis. Our results will significantly add to our knowledge of how structures required for vision are formed by modification of the actin cytoskeleton.

描述（由申请人提供）：要了解形态发生，必须知道肌动蛋白细胞骨架如何形成以及如何拆开。目前，人们对发展中的动物是如何发生的，而在发育中的眼中却少了。我们的目标是将光线带入眼睛研究领域，增强我们可视化肌动蛋白细胞骨架的能力，如何调节眼睛的形态发生。我们将使用果蝇Meianogaster作为模型系统采用遗传方法。我们一直在研究Twinstar（TSR）基因，该基因是Cofilin的果蝇同源物，该蛋白质在重新组织肌动蛋白细胞骨架中具有重要作用。我们已经表明，TSR是卵巢发育过程中细胞运动所必需的。我们还能够证明，通过使用我们开发的称为阻遏物敏感（RS）突变的遗传技术，在视网膜的形态发生过程中需要进行TSR。通过TSR RS突变，我们可以在眼睛发育后期特别抑制TSR的表达，从而使我们能够在此阶段研究TSR的作用，而不必担心TSR在其他组织或其他发育时期的影响。我们的结果表明，TSR对于横纹肌的适当发展以及视网膜伸长是必需的。现在，我们建议继续分析TSR在眼部形态发生过程中的作用，并使用RS突变技术研究眼睛形态发生过程中其他肌动蛋白细胞骨架调节基因的作用，包括lim激酶的果蝇同源物，肌动蛋白相互作用的蛋白质1（AIP 1（AIP 1）（AIP 1）（AIP 1），PAK，RAC，RAC和ARP2/3。我们还将筛选出在眼睛形态发生后期与TSR相互作用的新型基因。我们的结果将大大增加我们对视力所需的结构的了解，如何通过肌动蛋白细胞骨架的修饰形成。