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.

项目概要 视觉信息通过专门的通道进行处理： 在果蝇的每个小眼中 视网膜，运动由投射到层的六个“外部光感受器”处理，颜色由 光感受器 R7 和 R8 属于两种亚型：在 p 亚型中，pR7 表达紫外线敏感的 Rh3 和 pR8 在 y 亚型中，yR7 中的 UV-Rh4 与 yR8 中的 Green-Rh6 耦合。 将该信息从 R7 传递到 R8 以协调视紫红质的表达（目标 1）。 我们将把这项工作扩展到来自外部光感受器的信号，这些信号控制着光感受器的分裂 椎板前体细胞（LPC）通过释放 Hedgehog 来诱导椎板神经元的分化 L1-L5 通过从其末端释放 EGF/Spitz 在目标 2 中，我们将确定如何发育。 光感受器及其层目标的协调。 我们还发现，不同的神经胶质细胞类型在五个层细胞的模式中发挥着特定的作用 这让我们研究神经胶质细胞如何起源于视叶的不同区域，以及它们如何迁移到。 采取它们的最终位置，以及它们如何向 L1-L5 传递分化信号（目标 3）。 目标 1. 通过 R7 光感受器的信号来确定 R8 亚型的命运 我们将分析 R8 亚型的命运。 参与 R7-R8 通讯的多个 BMP/激活素配体的重要性，并测试它们是否 R8 中的信号通过涉及疣肿瘤的双稳态环得到增强。 抑制剂和生长调节剂 Melted 我们将确定 Mad/Smad2 是否激活 Melted 或抑制。 疣，生成并维持正确的小眼 R7 和 R8 亚型。 BMP/激活素信号仅限于单个小眼，并且不会扩散到邻近的小眼We。 已经表明 Hibris 细胞粘附分子限制了这种扩散，并将研究它如何影响 R7-R8 配对。 扩大的信号扩散会产生 Rh5 R8 簇，这让人想起眼睛中的色素沉着簇。 我们将利用我们的进化-发育专业知识来研究信号如何在特定物种中传播。 目标 2：来自光感受器的信号如何指定层的五种细胞类型？ 来自外部光感受器的信号调节增殖和细胞周期退出以产生层板前体。 然后我们将操纵 EGFR 来了解光感受器的 Spitz 水平如何影响层分化。 测试层板前体中的 EGFR/Notch 拮抗作用如何促进 L1-L5 多样化。 目标 3. 不同神经胶质细胞群对层状神经元规范的作用 我们有证据表明。 层细胞决定的顺序和动力学与神经胶质细胞的发育相结合我们将操纵神经胶质细胞。 使用基因组学来确定细胞如何参与介导光感受器的 EGF 信号。 通过实时成像，我们将描述不同神经胶质细胞群的特征并确定它们的起源，然后我们将进行开发。 有助于指定层神经元多样性的相互作用的定量和预测模型。