OMMATIDIAL PATTERNING DURING EYE DEVELOPMENT

眼睛发育过程中的视觉模式

• 批准号: 6708039
• 负责人: Marek Mlodzik
• 金额: $ 42.38万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6708039
• 关键词: Drosophilidae; Xenopus; biological signal transduction; cell differentiation; cellular polarity; genetically modified animals; glycoproteins; growth /development; neural information processing; protein binding; protein kinase C; protein structure function; receptor binding; receptor expression; visual photoreceptor; yeast two hybrid system

DESCRIPTION (Applicant's Description): The function of the visual system is to form images. Correct patterning of photoreceptor neurons in the retina is critical for their precise retinotopic axonal projections onto the optic lobes in the brain. Precise photoreceptor arrangement within the retinal epithelium is thus important. The Drosophila retina is a stereotyped pattern of about 800 ommatidia, or unit eyes, and the photoreceptor neurons within each ommatidium. The establishment of this precise arrangement serves as a paradigm to study epithelial planar polarity (often present in neuro-epithelial structures). It requires the Frizzled (Fz) receptor and its associated signaling pathway. Fz proteins are receptors for the Wg/Wnt growth factor family. Fz signaling regulates both early eye development and eye size, and the ommatidial arrangement within the retina. Fz uses distinct signaling pathways to achieve these different tasks. Wg/Fz signaling regulates eye size, whereas a distinct Fz-mediated signaling pathway regulates photoreceptor arrangement. It is important to achieve signaling specificity as these Fz functions lead to opposite responses: Wg/Fz signaling inhibits photoreceptor differentiation, whereas Fz/planar polarity signaling regulates the precise photoreceptor arrangement. The scope of this application is to identify the Fz domains that select between the two signaling cascades, and to identify the proteins that interact with the respective sequences. A combination of Drosophila in vivo studies and biochemical experiments will be used to achieve this goal. Several effectors of Fz have been identified and will be analyzed for their role in the selection between the two Fz signaling cascades. Wnt/Fz signaling has also been implicated in many forms of cancer and several of its components are proto-oncogenes. Thus the information acquired in this application will both advance our understanding of retinal patterning in the eye, and will also be of importance for the study of carcinogenesis.

描述（申请人的描述）：视觉系统的功能是 形成图像。视网膜中感光神经元的正确模式是 对于视网膜轴突在视叶上的精确投影至关重要 在大脑中。视网膜上皮内精确的感光器排列 因此很重要。果蝇视网膜有约800个定型图案 小眼，或单眼，以及每个小眼内的感光神经元。 这种精确安排的建立可以作为研究的范式 上皮平面极性（通常存在于神经上皮结构中）。它 需要卷曲 (Fz) 受体及其相关信号通路。 Fz 蛋白质是 Wg/Wnt 生长因子家族的受体。 Fz信号传导 调节早期眼睛发育和眼睛大小，以及小眼 视网膜内的排列。 Fz 使用不同的信号通路来实现 这些不同的任务。 Wg/Fz 信号传导调节眼睛大小，而独特的 Fz 介导的信号通路调节光感受器排列。这是 对于实现信号特异性很重要，因为这些 Fz 功能会导致 相反的反应：Wg/Fz 信号传导抑制光感受器分化， 而 Fz/平面极性信号调节精确的光感受器 安排。此应用程序的范围是识别 Fz 域 在两个信号级联之间进行选择，并识别出 与各自的序列相互作用。果蝇体内的组合 研究和生化实验将用于实现这一目标。一些 Fz 的效应器已被识别，并将对其在 两个 Fz 信号级联之间的选择。 Wnt/Fz 信号也已被 与许多形式的癌症有关，其几个组成部分是 原癌基因。因此，在此应用程序中获取的信息将 增进我们对眼睛视网膜图案的理解，也将有助于 对于癌变研究具有重要意义。