Late photoreceptor cell differentation in D melanogaster

黑腹果蝇感光细胞晚期分化

• 批准号: 6858530
• 负责人: BERTRAND MOLLEREAU
• 金额: $ 29.23万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6858530
• 关键词: Drosophilidae; cell differentiation; cell morphology; cell type; cytogenetics; developmental genetics; electron microscopy; gene expression; green fluorescent proteins; histogenesis; in situ hybridization; phenotype; polymerase chain reaction; regulatory gene; rhodopsin; southern blotting; visual photoreceptor

The long-term goal of this proposal is to understand the molecular and cellular mechanisms, which allow the acquisition of the terminal photoreceptor cell (PR) fate. The formation of PR's in Drosophila melanogaster serves as a paradigm to understand cell type determination and differentiation. During larval stages, an exquisitely precise series of sequential inductive processes leads to the recruitment of eight PR's in each ommatidium. However, their final differentiation, including rhabdomere morphogenesis and opsin expression is only completed three days later during pupal development. It is thought that PR cell fate is irreversibly established during larval development, when each PR expresses a particular set of transcriptional regulators. The PI's preliminary studies show that spalt complex genes are required late for the establishment of rhabdomere morphology and opsin expression in inner PR's, but not for their correct projection to the optic lobe. These data indicate that PR differentiation occurs as a two-step process under different genetic regulation. The following specific aims are proposed to further understand the mechanisms involved in the terminal differentiation processes: The role of the spalt genes in terminal PR differentiation will be addressed by analyzing (1) the loss-of-function phenotype of individual spalt genes (spalt major and spalt related); (2) the gain-of-function phenotype induced by the misexpression of the spalt genes. (3) Genetic interactions between spalt and otd, another gene involved in terminal PR differentiation, will be addressed. (4) The identification of downstream targets of spalt will be carried out by testing the role of genes that we previously identified to be expressed in inner PR's. The overall strategy of retinal cell fate determination and differentiation is the same in vertebrate and Drosophila retina, as are many of the factors employed. The understanding of how retinal cells adopt their final cell shape and structures is of obvious significance to developmental processes and to many human retinal diseases.

该提案的长期目标是了解分子和细胞机制，从而获得终末感光细胞（PR）的命运。 果蝇中 PR 的形成是理解细胞类型决定和分化的范例。 在幼虫阶段，一系列极其精确的连续诱导过程导致每个小眼中招募八个 PR。 然而，它们的最终分化，包括横纹肌形态发生和视蛋白表达，仅在三天后的蛹发育过程中完成。 人们认为，PR 细胞的命运在幼虫发育过程中不可逆转地确定，此时每个 PR 都表达一组特定的转录调节因子。 PI 的初步研究表明，后期需要 spalt 复合体基因来建立弹状体形态和内部 PR 中的视蛋白表达，但不需要它们正确投射到视叶。 这些数据表明 PR 分化在不同的遗传调控下作为两步过程发生。 为了进一步了解终末分化过程中涉及的机制，提出以下具体目标： 通过分析（1）单个 spalt 基因（spalt 主要基因和 spalt 相关基因）的功能丧失表型来解决 spalt 基因在终末 PR 分化中的作用； (2) spalt基因的错误表达诱导的功能获得表型。 (3) 将解决 spalt 和 otd（另一个参与 PR 终末分化的基因）之间的遗传相互作用。 (4) spalt下游靶标的鉴定将通过测试我们之前鉴定的在内部PR中表达的基因的作用来进行。 脊椎动物和果蝇视网膜中视网膜细胞命运决定和分化的总体策略是相同的，所采用的许多因素也是如此。 了解视网膜细胞如何形成最终的细胞形状和结构对于发育过程和许多人类视网膜疾病具有明显的意义。