Signaling from photoreceptors to the optic lobes

从光感受器到视叶的信号传递

• 批准号: 9336927
• 负责人: Claude Desplan
• 金额: $ 39.63万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9336927
• 关键词: Activins; Address; Affect; Biological Models; Bypass; Cell Adhesion Molecules; Cell Cycle; Cell Proliferation; Cells; Color; Color Visions; Communication; Computer Simulation; Cone; Coupled; Development; Diffuse; Diffusion; Drosophila genus; EGF gene; Ensure; Epidermal Growth Factor Receptor; Erinaceidae; Eye; Feedback; Genetic; Genetic Transcription; Genomics; Growth; Image; Individual; Investigation; Kinetics; Ligands; Light; Mediating; Morphogenesis; Motion; Neuroglia; Neurons; Optic Lobe; Pathway interactions; Pattern; Photoreceptors; Pigmentation physiologic function; Pigments; Play; Population; Positioning Attribute; Process; Regulation; Retina; Rhodopsin; Role; Sensory; Signal Transduction; Specific qualifier value; Testing; To specify; Transforming Growth Factor beta; Tumor Suppressor Proteins; UV sensitive; Vertebrates; Work; absorption; bone morphogenetic protein receptors; cell determination; cell fate specification; cell type; experimental study; fly; glial cell development; information processing; insight; melting; nerve supply; notch protein; novel; organ growth; precursor cell; predictive modeling; receptor; retinal rods; sensory system; visual information; visual performance

Project summary Visual information is processed through specialized channels: In each ommatidium of the Drosophila retina, motion is processed by the six ‘outer photoreceptors’ that project to the lamina. Color is detected by photoreceptors R7 and R8 that belong to two subtypes: In the p subtype, pR7 expresses UV-sensitive Rh3 and pR8 contains Blue-Rh5. In the y subtype, UV-Rh4 in yR7 is coupled to Green-Rh6 in yR8. We offer to study the signal that relays this information from R7 to R8 to coordinate the expression of Rhodopsins (Aim 1). We will extend this work to the signals originating from outer photoreceptors, which control the division of lamina precursor cells (LPCs) by releasing Hedgehog, and which induce the differentiation of the lamina neurons L1-L5 by releasing EGF/Spitz from their termini. In Aim 2, we will determine how the development of photoreceptors and of their lamina targets is coordinated. We also discovered that distinct glial cell types play specific roles in patterning each of the five lamina cell types. This has prompted us to study how glia originate in different regions of the optic lobes, how they migrate to take on their final positions, and how they mediate differentiation signals to L1-L5 (Aim 3). Aim 1. Specification of the R8 subtype fate by signaling from R7 photoreceptors. We will analyze the significance of multiple BMP/Activin ligands that participate in R7-R8 communication, and test whether they signal through their canonical receptors. The signal is reinforced in R8 by a bistable loop involving the Warts tumor suppressor and a growth regulator, Melted. We will determine whether Mad/Smad2 activate melted or repress warts, to generate and maintain the correct ommatidial R7 and R8 subtypes. The BMP/Activin signals are restricted to a single ommatidium, and do not diffuse to neighboring ommatidia. We have shown that the Hibris cell adhesion molecule limits this diffusion and will study how it affects R7-R8 pairing. Expanded signal diffusion leads to clusters of Rh5 R8s that are reminiscent of clusters of pigmentation in the eye of Eristalinus flies. We will use our evo-devo expertise to study how the signal may be propagated in specific species. Aim 2: How do signals from photoreceptors specify the five cell types of the lamina? We will explore how signals from the outer photoreceptors regulate proliferation and cell cycle exit to generate lamina precursors. We will then manipulate EGFR to ask how Spitz levels from photoreceptors affect lamina differentiation. We will also test how EGFR/Notch antagonism among lamina precursors contributes to L1-L5 diversification. Aim 3. The role of different glial populations for the specification of lamina neurons. We have evidence that the order and kinetics of lamina cell determination is coupled with glial development. We will manipulate glial cells to determine how they are involved in mediating the EGF signal from photoreceptors. Using genomics and live imaging, we will characterize the different populations of glia and determine their origin. We will then develop a quantitative and predictive model of the interactions that contribute to specifying lamina neuronal diversity.

项目摘要 视觉信息是通过专门的渠道处理的：在果蝇的每个膜中 视网膜，运动是由向层片的六个“外部光感受器”处理的。颜色被检测到 属于两个亚型的光感受器R7和R8：在P亚型中，PR7表达紫外线敏感RH3和PR8 包含蓝色RH5。在Y子类型中，YR7中的UV-RH4与YR8中的绿色RH6耦合。我们提出研究信号 将这些信息从R7转到R8以协调视紫红蛋白的表达（AIM 1）。 我们将将这项工作扩展到源自外部光感受器的信号，这些信号控制了划分 通过释放刺猬，并诱导椎板神经元的分化来通过椎板前体细胞（LPC） L1-L5通过从其末端释放EGF/Spitz。在AIM 2中，我们将确定如何发展 光感受器及其椎板靶标的协调。 我们还发现，不同的神经胶质细胞类型在构图五个薄片细胞中的每一个中都起着特定的作用 类型。这促使我们研究了神经胶质如何起源于视觉爱的不同区域，它们如何迁移到 执行他们的最终位置，以及如何介导分化信号到L1-L5（AIM 3）。 AIM 1。通过来自R7光感受器的信号传导R8亚型命运的规范。我们将分析 参与R7-R8通信的多种BMP/活化素配体的重要性，并测试它们是否 通过其规范受体发出信号。信号通过涉及疣肿瘤在R8中加强R8 抑制剂和生长调节剂融化。我们将确定MAD/SMAD2是激活融化还是复制品 疣，生成和维护正确的Ommatidial R7和R8亚型。 BMP/活化素信号仅限于单个蛋白膜，并且不会扩散到相邻的蛋白膜上。我们 已经表明，Hibris细胞依从性分子限制了这种扩散，并将研究其如何影响R7-R8配对。 扩展的信号扩散导致RH5 R8的簇，这些簇想起了眼睛的色素沉着簇 Eristalinus苍蝇。我们将使用我们的EVO-DEVO专业知识来研究如何以特定规格传播信号。 AIM 2：来自光感受器的信号如何指定薄片的五种细胞类型？我们将探讨如何 来自外部光感受器的信号调节增殖和细胞周期出口以产生椎板前体。我们 然后，将操纵EGFR以询问来自感光体的Spitz水平如何影响层层分化。我们也会 测试椎板前体之间的EGFR/Notch拮抗作用如何有助于L1-L5多样化。 AIM 3。不同神经胶质种群在椎板神经元规范中的作用。我们有证据表明 椎板细胞测定的顺序和动力学与神经胶质发育相结合。我们将操纵神经胶质 细胞确定它们如何参与从感光体中介导EGF信号的情况。使用基因组学和 实时成像，我们将表征不同的神经胶质种群并确定其起源。然后我们将发展 相互作用的定量和预测模型，有助于指定椎板神经元多样性。