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被分解的。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发生的情况就更少了。我们的目标是为眼睛研究的这一领域带来光明，提高我们可视化眼睛形态发生过程中肌动蛋白细胞骨架是如何被调节的能力。我们将采用遗传方法，以果蝇为模型系统。我们一直在研究双星（tsr）基因，这是果蝇同源的cofilin，在重组肌动蛋白细胞骨架中起主要作用的蛋白质。我们已经证明，tsr是卵巢发育过程中细胞运动所必需的。我们也已经能够证明，tsr在视网膜的形态发生过程中是必需的，通过使用一种我们开发的基因技术，称为抑制因子敏感（RS）突变。通过tsr RS突变，我们可以在眼睛发育后期特异性地抑制tsr的表达，使我们能够研究tsr在这一阶段的作用，而无需考虑tsr在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延伸所必需的。我们建议继续分析tsr在眼睛形态发生中的作用，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睛形态发生中的作用，包括果蝇的LIM激酶、肌动蛋白相互作用蛋白1 （Aip 1）、PAK、rac和Arp2/3复合物。我们还将筛选在眼睛形态发生后期与tsr基因相互作用的新基因。我们的结果将显著地增加我们的知识所需的视觉结构是如何通过修改肌动蛋白细胞骨架形成的。

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.