Late photoreceptor cell differentation in D melanogaster

黑腹果蝇感光细胞晚期分化

• 批准号: 6465533
• 负责人: BERTRAND MOLLEREAU
• 金额: $ 32.13万
• 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 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6465533
• 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，这些机制允许获得末端感光细胞（PR）命运。 果蝇中PR的形成是了解细胞类型的测定和分化的范例。 在幼虫阶段，一系列精确的顺序感应过程导致每个膜中的八个PR募集。 然而，它们的最终分化，包括横纹肌形态发生和Opsin表达，仅在三天后才能完成。 人们认为，当每个PR表达一组特定的转录调节剂时，PR细胞命运是在幼虫发育过程中不可逆转的。 PI的初步研究表明，在内PR中建立横纹肌形态和OPSIN表达需要较晚的Spalt复合基因，但不是因为它们正确投影对视觉叶。 这些数据表明，在不同的遗传调节下，PR分化是作为两步过程的。 提出了以下具体目的，以进一步了解终端分化过程中涉及的机制：通过分析（1）单个Spalt基因的功能丧失表型（Spalt Major和Spalt与Spalt相关），将解决Spalt基因在末端分化中的作用； （2）由Spalt基因的Misexpression诱导的功能型表型。 （3）将解决Spalt和OTD之间的遗传相互作用，这是末端PR分化的另一个基因。 （4）将通过测试我们先前确定在内PR中表达的基因的作用来实现SPALT的下游靶标的识别。 在脊椎动物和果蝇视网膜中，视网膜细胞命运的确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。 对视网膜细胞如何采用其最终细胞形状和结构的理解对发育过程和许多人类视网膜疾病具有明显的意义。