Late photoreceptor cell differentation in D melanogaster

本提案的长期目标是了解分子和细胞机制，这使得获得终端光感受器细胞（PR）的命运。黑腹果蝇中PR's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，一系列非常精确的顺序诱导过程导致每个小囊中招募8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，只在蛹发育3天后完成。人们认为PR细胞的命运在幼虫发育过程中是不可逆的，每个PR表达一组特定的转录调节因子。PI的初步研究表明，在横纹肌形态的建立和内PR的视蛋白表达方面，spalt复杂基因是后期需要的，而不是它们正确地投射到视叶。这些数据表明，在不同的遗传调控下，PR分化是一个两步走的过程。为了进一步了解末端分化过程的机制，我们提出了以下具体目标：通过分析(1)单个spalt基因（spalt主基因和spalt相关基因）的功能缺失表型来解决spalt基因在末端PR分化中的作用；(2) spalt基因错表达诱导的功能获得表型。(3)研究spalt与另一个参与末端PR分化的基因otd之间的相互作用。(4) spalt下游靶点的鉴定将通过检测我们之前确定的在内部PR中表达的基因的作用来进行。在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，正如许多被采用的因素一样。了解视网膜细胞如何形成其最终的细胞形状和结构，对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.