Regulation of Eye Morphogenesis

眼睛形态发生的调节

• 批准号: 6912716
• 负责人: FRANK LASKI
• 金额: $ 37.6万
• 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/6912716
• 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）：为了理解形态发生，必须知道肌动蛋白细胞骨架如何形成以及如何分解。目前，人们对发育中的动物如何发生这种情况知之甚少，而在发育中的眼睛中则知之甚少。我们的目标是为眼睛研究这一领域带来光明，提高我们可视化肌动蛋白细胞骨架在眼睛形态发生过程中如何调节的能力。我们将采用遗传方法，使用黑腹果蝇作为模型系统。我们一直在研究 twinstar (tsr) 基因，它是果蝇 cofilin 的同源物，cofilin 是一种在重组肌动蛋白细胞骨架中起重要作用的蛋白质。我们已经证明，在卵巢发育过程中，tsr 是细胞运动所必需的。通过使用我们开发的称为阻遏物敏感（RS）突变的遗传技术，我们还能够证明 tsr 在视网膜的形态发生过程中是必需的。通过 tsr RS 突变，我们可以在眼睛发育的后期特异性抑制 tsr 的表达，使我们能够研究 tsr 在这个阶段的作用，而不用担心 tsr 对其他组织或其他发育时期的影响。我们的结果表明，tsr 是横纹肌正常发育和视网膜伸长所必需的。我们现在建议继续分析tsr在眼形态发生过程中的作用，并利用RS突变技术研究其他肌动蛋白细胞骨架调控基因在眼形态发生过程中的作用，包括LIM激酶的果蝇同源物肌动蛋白相互作用蛋白1（Aip 1)、PAK、rac 和 Arp2/3 复合体。我们还将筛选在眼睛形态发生后期与 tsr 发生遗传相互作用的新基因。我们的结果将显着增加我们对如何通过修饰肌动蛋白细胞骨架来形成视觉所需的结构的了解。