Function of the Six and Eya Genes in Retinal Development

Six 和 Eya 基因在视网膜发育中的功能

基本信息

  • 批准号:
    7110936
  • 负责人:
  • 金额:
    $ 32.16万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-08-01 至 2008-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): One of the most exciting revelations in retinal biology is that the molecules and mechanisms that direct eye formation are conserved throughout the animal kingdom. In recent years an entire cascade of molecules and their roles in eye specification have been found to be preserved in both mammalian and invertebrate retinal systems. In addition to provoking a profound rethinking of the origins of the eye, the emerging commonality among mechanisms used in eye development allows for the use of model systems to provide insight into the development and diseases of the mammalian eye. The Sine oculis box (Six) and Eyes absent (Eya) gene families function within the signaling cascades that regulate eye and head development in both mammals and invertebrates. Bilateral anophthalmia and holoprosencephaly type 2 are caused by mutations within the human Six6 and Six3 genes, while molecular lesions within the human Eyal gene result in congenital cataracts, Branchio-Oto-Renal (BOR) and Oto-FaciaI-Cervial (OFC) syndromes. The association of Six and Eya gene lesions with eye diseases, provides us with an exciting opportunity to explore the roles played by the SIX and EYA proteins in retinogenesis. The developing eye of the fruit fly, Drosophila melanogaster, is an excellent experimental system for elucidating the genetic, molecular and biochemical mechanisms underlying the activities of the SIX and EYA proteins. In the fruit fly, the Six family is represented by the SINE OCULIS (SO) and OPTIX proteins, while the EYES ABSENT (EYA) protein is the only Eya family member. The goals of the proposed work are (1) to identify the steps in eye specification that are regulated by the Drosophila SIX and EYA family members; (2) to define the functional differences between the two fruit fly SIX proteins; (3) to understand the interactions of several signaling pathways with SO; and (4) to identify additional genes whose products participate in eye development and interact with SO. To achieve these goals, eye development will be analyzed in animals lacking both SO and EYA proteins; biochemical approaches will be used to dissect functional differences between SO and OPTIX; and the well-established techniques of Drosophila genetics will be used to define relationships between SO and other key proteins involved in eye development. Together, these approaches will provide insight into the roles of the SIX and EYA proteins in eye specification.
描述(由申请人提供):视网膜生物学中最令人兴奋的发现之一是,指导眼睛形成的分子和机制在整个动物界中都是保守的。近年来,人们发现哺乳动物和无脊椎动物的视网膜系统中都保留了整个分子级联及其在眼睛规范中的作用。除了引发对眼睛起源的深刻反思之外,眼睛发育中使用的机制之间出现的共性允许使用模型系统来深入了解哺乳动物眼睛的发育和疾病。眼正弦盒(Sine oculus box,Six)和眼睛缺失(Eya)基因家族在调节哺乳动物和无脊椎动物眼睛和头部发育的信号级联中发挥作用。双侧无眼症和 2 型前脑无裂畸形是由人类 Six6 和 Six3 基因内的突变引起的,而人类 Eyal 基因内的分子损伤会导致先天性白内障、鳃-耳-肾 (BOR) 和耳-面-颈 (OFC) 综合征。 Six 和 Eya 基因病变与眼部疾病的关联为我们提供了一个令人兴奋的机会来探索 SIX 和 EYA 蛋白在视网膜发生中所起的作用。果蝇(Drosophila melanogaster)正在发育的眼睛是阐明 SIX 和 EYA 蛋白活性背后的遗传、分子和生化机制的绝佳实验系统。在果蝇中,Six 家族以 SINE OCULIS (SO) 和 OPTIX 蛋白为代表,而 EYES ABSENT (EYA) 蛋白是唯一的 Eya 家族成员。拟议工作的目标是(1)确定由果蝇 SIX 和 EYA 家族成员调节的眼睛规范步骤; (2) 明确两种果蝇SIX蛋白的功能差异; (3) 了解多种信号通路与SO的相互作用; (4) 鉴定其产物参与眼睛发育并与 SO 相互作用的其他基因。为了实现这些目标,将对缺乏 SO 和 EYA 蛋白的动物的眼睛发育进行分析;将使用生化方法来剖析 SO 和 OPTIX 之间的功能差异;成熟的果蝇遗传学技术将用于定义 SO 与其他参与眼睛发育的关键蛋白质之间的关系。总之,这些方法将深入了解 SIX 和 EYA 蛋白在眼睛规范中的作用。

项目成果

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Justin P Kumar其他文献

Justin P Kumar的其他文献

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{{ truncateString('Justin P Kumar', 18)}}的其他基金

Induction of retinal development by the peripodial epithelium in Drosophila
果蝇足周上皮诱导视网膜发育
  • 批准号:
    10190594
  • 财政年份:
    2020
  • 资助金额:
    $ 32.16万
  • 项目类别:
Induction of retinal development by the peripodial epithelium in Drosophila
果蝇足周上皮诱导视网膜发育
  • 批准号:
    10570224
  • 财政年份:
    2020
  • 资助金额:
    $ 32.16万
  • 项目类别:
Induction of retinal development by the peripodial epithelium in Drosophila
果蝇足周上皮诱导视网膜发育
  • 批准号:
    10093048
  • 财政年份:
    2020
  • 资助金额:
    $ 32.16万
  • 项目类别:
Induction of retinal development by the peripodial epithelium in Drosophila
果蝇足周上皮诱导视网膜发育
  • 批准号:
    10356811
  • 财政年份:
    2020
  • 资助金额:
    $ 32.16万
  • 项目类别:
Function of the Six and Eya Genes in Retinal Development
Six 和 Eya 基因在视网膜发育中的功能
  • 批准号:
    8694777
  • 财政年份:
    2003
  • 资助金额:
    $ 32.16万
  • 项目类别:
Repression of Non-Ocular Fates by the SIX and EYA Genes During Specification and Patterning of the Retina
视网膜规范和图案化过程中 SIX 和 EYA 基因对非眼命运的抑制
  • 批准号:
    9135417
  • 财政年份:
    2003
  • 资助金额:
    $ 32.16万
  • 项目类别:
Function of the Six and Eya Genes in Retinal Development
Six 和 Eya 基因在视网膜发育中的功能
  • 批准号:
    7885124
  • 财政年份:
    2003
  • 资助金额:
    $ 32.16万
  • 项目类别:
Function of the Six and Eya Genes in Retinal Development
Six 和 Eya 基因在视网膜发育中的功能
  • 批准号:
    6669280
  • 财政年份:
    2003
  • 资助金额:
    $ 32.16万
  • 项目类别:
Function of the Six and Eya Genes in Retinal Development
Six 和 Eya 基因在视网膜发育中的功能
  • 批准号:
    6781741
  • 财政年份:
    2003
  • 资助金额:
    $ 32.16万
  • 项目类别:
Function of the Six and Eya Genes in Retinal Development
Six 和 Eya 基因在视网膜发育中的功能
  • 批准号:
    8265287
  • 财政年份:
    2003
  • 资助金额:
    $ 32.16万
  • 项目类别:
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