GENETIC CONTROL OF EYE SPECIFICATION

眼睛规格的基因控制

• 批准号: 6525184
• 负责人: FRANCESCA PIGNONI
• 金额: $ 25.9万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-05 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6525184
• 关键词: Drosophilidae; X ray; alleles; developmental genetics; eye; gene expression; gene interaction; genetic mapping; genetic regulation; genetic regulatory element; genetic transcription; histogenesis; molecular cloning; nucleic acid probes; phenotype; protein protein interaction; transcription factor; transposon /insertion element; yeast two hybrid system

DESCRIPTION (Verbatim from applicant's abstract): The long-term objective of this proposal is to gain a better understanding of the genetic control of eye-tissue determination in Drosophila. Several genes that play important roles in this process have been identified in recent years. These are the genes eyeless (ey), sine oculis (so), eyes absent (eya) and dachshund (dac). These genes are required for eye development, can induce other tissues to form eyes, and are linked in a gene network by interactions at the level of protein-protein contacts and transcriptional regulation. In order to generate a more complete picture of thegenetic circuitry involved in establishing eye identity in the fruit fly, we propose to identify additional genes involved in this process and study their relationship to the genes already known. We are pursuing four different approaches to identify novel factors involved in this process. In the first two approaches, we make use of previously identified components of the eye-specification gene network to identify novel factors through protein-DNA and protein-protein interactions. The other twoarebased on genetic screens to identify gene activities required or sufficient for eye induction within theeye disc (normal eyes) or in other tissues (ectopic eyes). A detailed molecular and functional characterization of the genes identified using these approaches will be carried out. Through a combination of forward genetic and reverse genetic approaches, molecular genetic analysis and ectopic expression studies, we will dissect the function of these novel factors in eye-tissue specification and define their role in the context of the already identified genetic pathways, Interestingly, despite the significant differences in structure and function between the fly and human eyes, the components of this genetic network appear to be evolutionarily conserved. Several related genes have been identified in mouse and humans including Pax6 and multiple Six, Eya and Dac genes and some of these genes have been found to regulate eye development in vertebrates. Thus, mutations in eyeless Pax6 cause Aniridia inhumans, the Small eye phenotype in mice, and the eyeless phenotype in Drosophila. Moreover, Pax6 and Six3 have been shown to induce eye structures (lens and retina) when ectopically expressed in Xenopus and Medaka fish, indicating that the homology at the molecular level may extend to a conservation of function in eye development. The extensive conservation of molecular factors involved in the early steps of eye development indicates that work in Drosophila will provide insights into the genetic mechanisms controlling mammalian eye development.

描述（来自申请人摘要的逐字记录）： 这一建议是为了更好地了解遗传控制， 果蝇的眼组织测定。几个基因发挥着重要作用 在这一过程中，近年来已经确定。这些基因 无眼（eyeless），无眼（sine oculis），无眼（eyes absent），腊肠（dachshund）。这些 基因是眼睛发育所必需的，可以诱导其他组织形成眼睛， 在基因网络中通过基因水平上的相互作用 蛋白质-蛋白质接触和转录调节。以便生成 更完整的关于眼睛形成的遗传线路的图片 在果蝇的身份，我们建议确定其他基因参与 这个过程并研究它们与已知基因的关系。我们 采用四种不同的方法来确定参与其中的新因素， 过程在前两种方法中，我们利用先前确定的 眼特异性基因网络的组成部分，以确定新的因素 通过蛋白质-DNA和蛋白质-蛋白质相互作用。另外两个是基于 基因筛选，以确定眼睛所需或足够的基因活性 眼盘内（正常眼）或其他组织（异位眼）的诱导。 鉴定的基因的详细分子和功能特征 将使用这些方法。通过结合前进 遗传和反向遗传方法，分子遗传分析和异位 表达的研究，我们将剖析这些新的因素， 眼组织规范，并定义其作用的背景下，已经 确定了遗传途径，有趣的是，尽管有显着差异， 在结构和功能上，果蝇和人眼之间， 这个遗传网络似乎是进化保守的。几个相关 已经在小鼠和人类中鉴定出包括Pax 6和多种Six的基因， Eya和Dac基因，其中一些基因已被发现调节眼睛 脊椎动物的发育。因此，无眼Pax 6突变导致无虹膜 人类中的小眼表型，小鼠中的小眼表型，以及人类中的无眼表型。 果蝇此外，Pax 6和Six 3已被证明诱导眼结构 (lens和视网膜）在非洲爪蟾和青鳉鱼中异位表达时， 这表明在分子水平上的同源性可以延伸到 保护眼睛发育的功能。大规模保护 参与眼睛发育早期阶段的分子因素表明， 在果蝇中的工作将提供对遗传机制的深入了解， 控制着哺乳动物眼睛的发育