Regulation of Eye Morphogenesis

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是如何形成的，以及它是如何分解的。目前，关于这种情况如何发生在发育中的动物身上鲜为人知，在发育中的眼睛中发生的更少。我们的目标是为眼睛研究的这一领域带来曙光，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是如何调节的能力。我们将采用遗传学的方法，以巨型果蝇为模型系统。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方面发挥重要作用的蛋白质。我们已经证明，在卵巢发育过程中，TSR是细胞运动所必需的。我们还利用我们开发的一种称为抑制子敏感(RS)突变的基因技术，证明了TSR在视网膜的形态发生过程中是必需的。通过TSR RS突变，我们可以特异性地抑制TSR在眼睛发育后期的表达，使我们能够研究TSR在这个阶段的作用，而不需要考虑TSR在其他组织或其他发育阶段的影响。我们的结果表明，TSR对于横纹球的正常发育和视网膜的延长都是必需的。我们现在建议继续分析TSR在眼睛形态发生中的作用，并使用RS突变技术来研究其他肌动蛋白细胞骨架调控基因在眼睛形态发生中的作用，包括果蝇LIM激酶、肌动蛋白相互作用蛋白1(AIP 1)、PAK、RAC和Arp2/3复合体的同源基因。我们还将筛选在眼睛形态发生的后期阶段与TSR基因相互作用的新基因。我们的结果将大大增加我们对视觉所需结构是如何通过肌动蛋白细胞骨架的修饰而形成的知识。

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.