GENETIC CONTROL OF EYE SPECIFICATION

眼睛规格的基因控制

基本信息

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
项目类别：
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

项目摘要

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（申请人摘要的逐字记录）：长期目标该提议是为了更好地了解基因控制果蝇眼组织测定。几个发挥重要作用的基因近年来已确定了这一过程。这些是基因无眼 (ey)、正弦眼 (so)、无眼 (eya) 和腊肠犬 (dac)。这些眼睛发育需要基因，可以诱导其他组织形成眼睛，并通过以下水平的相互作用连接在基因网络中蛋白质-蛋白质接触和转录调控。为了生成一个更完整地了解参与形成眼睛的遗传回路在果蝇的身份中，我们建议鉴定参与的其他基因这个过程并研究它们与已知基因的关系。我们是采用四种不同的方法来识别与此相关的新因素过程。在前两种方法中，我们利用先前确定的眼睛特异性基因网络的组成部分来识别新因素通过蛋白质-DNA 和蛋白质-蛋白质相互作用。另外两个是基于遗传筛查，以确定眼睛所需或足够的基因活性在眼盘（正常眼）或其他组织（异位眼）内进行感应。已识别基因的详细分子和功能特征将使用这些方法进行。通过前向组合遗传和反向遗传方法、分子遗传分析和异位表达研究，我们将剖析这些新因子在眼组织规范并在已经存在的背景下定义它们的作用有趣的是，尽管存在显着差异，但确定了遗传途径在果蝇和人眼的结构和功能上，这个遗传网络似乎在进化上是保守的。几个相关的已在小鼠和人类中鉴定出基因，包括 Pax6 和多个 Six， Eya 和 Dac 基因以及其中一些基因被发现可以调节眼睛脊椎动物的发育。因此，无眼 Pax6 的突变会导致无虹膜症非人类、小鼠的小眼表型和无眼表型果蝇。此外，Pax6 和 Six3 已被证明可以诱导眼睛结构（晶状体和视网膜）当在爪蟾和青鳉鱼中异位表达时，表明分子水平上的同源性可能延伸至保护眼睛发育中的功能。广泛的保护参与眼睛发育早期步骤的分子因素表明果蝇的工作将提供对遗传机制的见解控制哺乳动物眼睛的发育。