Regulation of photoreceptor cell fate by rhomboid and hibris

菱形和 hibris 对感光细胞命运的调节

• 批准号: 7736166
• 负责人: STEVEN G BRITT
• 金额: $ 38.27万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7736166
• 关键词: Biological Models; Biological Neural Networks; Cells; Color; Color Visions; Complex; Development; Disease; Docking; Dorsal; Drosophila melanogaster; Epidermal Growth Factor Receptor; Event; Eye; Eye Development; Generations; Genes; Genetic; Health; Immunoglobulins; Individual; Maps; Molecular; Molecular Genetics; Nervous System Physiology; Notch Signaling Pathway; Organism; Pathway interactions; Pattern; Phase; Photoreceptors; Play; Population; Positioning Attribute; Process; Proto-Oncogene Proteins c-akt; Receptor Signaling; Regulation; Resolution; Retina; Retinal; Role; Sampling; Signal Pathway; Signal Transduction; Signal Transduction Pathway; System; Time; UV sensitive; Visual; Work; cell fate specification; cell type; computerized data processing; fly; gene function; insight; light intensity; melting; member; mutant; nephrin; notch protein; programs; public health relevance; research study; retinotopic; rhomboid; sensory system

DESCRIPTION (provided by applicant): Cell-fate specification plays an essential role in the ultimate function of the nervous system. Generation of diverse cell populations and the regulation of their precise placement and connectivity patterns establishes neural networks capable of detecting, processing and sending complex signals. Cell identity, position and connectivity are especially important in sensory systems because of the added complexity of spatial information that must be detected and encoded. High-resolution sampling of visual space by the retina demands a dense array of photoreceptor cells sensitive to a wide dynamic range of light intensities. Moreover, color vision requires photoreceptor cells having different spectral sensitivities in addition to a precise retinotopic map. Currently, little is known about the generation of photoreceptor cell diversity or the specification of different spectral types. Drosophila melanogaster is capable of color vision and is a useful experimental system for examining the developmental programs that produce photoreceptor cells having different color sensitivities. We have found that a very specific inductive signal between adjacent photoreceptor cells coordinates their fates and color sensitivities. We have identified a large group of genes that influence this inductive signal. These genes include members of the Epidermal Growth Factor Receptor, nephrin related immunoglobulin superfamily (IgSF), and Notch signaling pathways. The aim of this proposal is to determine how the individual members of these signal transduction pathways function to establish photoreceptor cell-type adjacency and pairing, and to examine how these pathways interact in a coordinated way to regulate the inductive signal between adjacent photoreceptors. This work will provide a better understanding for how specific developmental signals operate during eye development and establish the patterned photoreceptor cell mosaic that is capable of color vision. PUBLIC HEALTH RELEVANCE: In our previous work, we have identified a group of genes that are required to establish the precise cell-cell adjacency of the R7 and R8 cell types in pale and yellow ommatidia. The purpose of this proposal is to define how each of the individual genes function in this process and to determine how they interact with each other overall. Because the molecular mechanisms that regulate eye development in different organisms are highly conserved, we believe that using Drosophila melanogaster as a model system to identify and characterize the genes responsible for photoreceptor cell patterning will provide important information that will be relevant to retina development in general. Furthermore, we believe that our analyses of the integration of multiple signal transduction pathways will also provide important insights that will be relevant to a variety of developmental and signaling processes in both health and disease.

描述（由申请方提供）：细胞命运特化在神经系统的最终功能中起着至关重要的作用。不同细胞群的产生及其精确位置和连接模式的调节建立了能够检测、处理和发送复杂信号的神经网络。细胞的身份、位置和连通性在感觉系统中尤其重要，因为必须检测和编码的空间信息增加了复杂性。视网膜对视觉空间的高分辨率采样需要对宽动态范围的光强度敏感的感光细胞的密集阵列。此外，色觉需要具有不同光谱灵敏度的光感受器细胞以及精确的视网膜定位图。目前，很少有人知道感光细胞的多样性或不同光谱类型的规格的产生。黑腹果蝇具有色觉能力，并且是用于检查产生具有不同颜色敏感性的感光细胞的发育程序的有用的实验系统。我们已经发现，相邻的感光细胞之间的一个非常具体的感应信号协调它们的命运和颜色敏感性。我们已经确定了一大组影响这种诱导信号的基因。这些基因包括表皮生长因子受体、nephrin相关免疫球蛋白超家族（IgSF）和Notch信号传导途径的成员。该建议的目的是确定这些信号转导通路的各个成员如何发挥作用以建立感光细胞类型的邻接和配对，并检查这些通路如何以协调的方式相互作用以调节相邻感光细胞之间的诱导信号。这项工作将提供一个更好的理解如何特定的发展信号在眼睛发育过程中运作，并建立图案化的感光细胞马赛克，能够颜色视觉。公共卫生相关性：在我们以前的工作中，我们已经确定了一组基因，这些基因是建立苍白和黄色小眼中R7和R8细胞类型的精确细胞-细胞邻接所必需的。这个建议的目的是定义每个基因在这个过程中如何发挥作用，并确定它们如何相互作用。由于调节眼睛发育的分子机制在不同的生物体是高度保守的，我们相信，使用果蝇作为一个模型系统，以确定和表征负责感光细胞图案的基因将提供重要的信息，这将是相关的视网膜发育一般。此外，我们相信，我们对多种信号转导途径整合的分析也将提供重要的见解，这些见解与健康和疾病中的各种发育和信号传导过程相关。