Late photoreceptor cell differentation in D melanogaster

这项提案的长期目标是了解分子和细胞机制，这使得获得终端感光细胞（PR）的命运。 黑腹果蝇中PR的形成可以作为理解细胞类型决定和分化的范例。 在幼虫阶段，一个精致精确的一系列顺序诱导过程导致招聘的8个PR的每个小眼。 然而，它们的最终分化，包括横纹肌形态发生和视蛋白表达，仅在蛹发育的三天后完成。 据认为，PR细胞的命运是不可逆的幼虫发育过程中建立的，当每个PR表达一组特定的转录调节因子。 PI的初步研究表明，spalt复合体基因是建立内部PR的横纹肌形态和视蛋白表达所必需的，但不是正确投射到视叶所必需的。 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。 提出以下具体目标以进一步了解终末分化过程中涉及的机制：将通过分析（1）单个spalt基因（spalt主要和spalt相关）的功能丧失表型来解决spalt基因在终末PR分化中的作用;（2）由spalt基因的错误表达诱导的功能获得表型。(3)spalt和otd之间的遗传相互作用，另一个基因参与终端PR分化，将被解决。(4)将通过测试我们先前鉴定为在内部PR中表达的基因的作用来鉴定spalt的下游靶标。 视网膜细胞命运决定和分化的总体策略在脊椎动物和果蝇视网膜中是相同的，所采用的许多因素也是相同的。 了解视网膜细胞如何采用其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。

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.