Genetic Control of Early Retinal Development

早期视网膜发育的基因控制

• 批准号: 7599534
• 负责人: Robert M Grainger
• 金额: $ 36.64万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-05 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7599534
• 关键词: Amphibia; Anterior; Area; Bioinformatics; Biological Assay; Biological Process; Chimera organism; Classification; Complex; Development; Embryo; Embryology; Erinaceidae; Event; Eye; Eye Development; Eye diseases; Family; Gene Expression; Gene Expression Regulation; Genes; Genetic; Goals; Homeobox Genes; Human; Laboratories; Location; Methods; Modeling; Molecular; Molecular Genetics; Operative Surgical Procedures; Pathway interactions; Pattern; Process; Property; Regulation; Regulator Genes; Regulatory Element; Retina; Retinal; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Staging; Stereotyping; System; Testing; Time; Tissues; Transcriptional Regulation; Transgenic Organisms; Ursidae Family; Visual Fields; Work; Xenopus; base; eye formation; gene interaction; genome sequencing; inhibitor/antagonist; member; neural plate; new technology; novel strategies; programs; relating to nervous system; research study; tool; transcription factor

DESCRIPTION (provided by applicant): While the study of the development of the retina, particularly the genes involved in its formation, is a very active area of study, the earliest processes leading to the formation of the retina remain poorly understood. It is the goal of this proposal to gain significant understanding of the primary mechanisms leading to determination of the embryonic retina in Xenopus embryos: how commitment to form the retina occurs and how the boundaries of this tissue are established. We wish to understand not only how the retina is formed, but also how it forms in such a precisely stereotyped manner since aberrations in this developmental program are implicated in a high fraction of genetically based eye diseases. Our work in recent years concerning this problem focus on four areas: 1) the embryology of eye development; 2) a systematic examination of the gene expression patterns of regulatory genes during the stages of eye determination; 3) extensive examination of the regulatory elements controlling key eye gene regulation (for example, the homeobox genes Rx, Pax6 and Six3); and 4) the development of new technology for study of gene regulation and manipulating gene expression in the Xenopus system. We propose three aims here. First we wish to define the key parameters that define the embryological state of determination of the retina, which occurs at approximately the neural plate stage, using embryological and molecular genetic assays to evaluate this process. Second we propose to examine the signaling pathways involved in retinal determination, focusing on the roles of Wnt, Hedgehog and IGF pathways in this process. Third, we will examine the regulation of and interactions among a critical group of transcription factors essential for retina formation in order to ascertain their roles in the determination mechanism.

描述（由申请人提供）：虽然对视网膜发育的研究，特别是涉及其形成的基因的研究是一个非常活跃的研究领域，但导致视网膜形成的最早过程仍然知之甚少。本研究的目标是对非洲爪蟾胚胎视网膜形成的主要机制有重要的了解：视网膜的形成是如何发生的，以及视网膜组织的边界是如何建立的。我们不仅希望了解视网膜是如何形成的，而且希望了解它是如何以如此精确的刻板方式形成的，因为这种发育程序中的畸变与很大一部分基于遗传的眼病有关。近年来，我们对这一问题的研究主要集中在四个方面：1)眼睛发育的胚胎学；2)系统地研究了眼决定阶段调控基因的基因表达模式；3)广泛检查控制关键眼睛基因调控的调控元件（例如，同源盒基因Rx， Pax6和Six3）；4)研究爪蟾系统基因调控和调控基因表达的新技术的发展。我们在此提出三个目标。首先，我们希望定义定义视网膜胚胎状态的关键参数，这发生在大约神经板阶段，使用胚胎学和分子遗传学分析来评估这一过程。其次，我们建议研究参与视网膜决定的信号通路，重点关注Wnt， Hedgehog和IGF通路在这一过程中的作用。第三，我们将研究视网膜形成所必需的一组关键转录因子之间的调控和相互作用，以确定它们在决定机制中的作用。