Regulation of photoreceptor cell fate by rhomboid and hibris

描述(由申请人提供)：细胞命运规范在神经系统的最终功能中起着至关重要的作用。不同细胞群体的产生及其精确放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大动态范围的光强度敏感的光感受器细胞的密集阵列。此外，色觉需要光感受器细胞具有不同的光谱敏感性，以及精确的视网膜定位图。目前，关于光感受器细胞多样性的产生或不同光谱类型的规范知之甚少。果蝇具有色觉能力，是检测产生具有不同颜色敏感度的感光细胞的发育程序的有用实验系统。我们发现，相邻感光细胞之间的一个非常特殊的感应信号协调了它们的命运和颜色敏感度。我们已经确定了一大组影响这种感应信号的基因。这些基因包括表皮生长因子受体、肾上腺素相关免疫球蛋白超家族(IgSF)和Notch信号通路的成员。这项建议的目的是确定这些信号转导通路中的单个成员如何发挥功能来建立光感受器细胞类型的邻接和配对，并研究这些通路如何以协调的方式相互作用来调节相邻光感受器之间的诱导信号。这项工作将更好地了解特定的发育信号在眼睛发育过程中是如何运作的，并建立具有颜色视觉能力的有图案的光感受器细胞马赛克。公共卫生相关性：在我们之前的工作中，我们已经确定了一组基因，这些基因是在苍白和黄色的小眼中建立R7和R8细胞类型的准确细胞-细胞邻接所必需的。这项提议的目的是定义每个单独的基因在这一过程中如何发挥作用，并确定它们总体上如何相互作用。由于在不同生物中调控眼睛发育的分子机制是高度保守的，我们相信使用黑腹果蝇作为模型系统来识别和表征负责光感受器细胞模式的基因将提供与视网膜发育总体相关的重要信息。此外，我们相信，我们对多个信号转导途径整合的分析也将提供重要的见解，这将与健康和疾病中的各种发育和信号过程相关。

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.