Induction of retinal development by the peripodial epithelium in Drosophila

项目概述：诱导，一个组织发出信号并影响其发展的过程。 另一个是后生动物发育的中心特征。一些最著名和研究最多的例子 包括发生在外胚层、中胚层和 在早期胚胎发育期间的内胚层。其他示例包括导致适当的 神经板、体节和脑发育。与这个建议相关的是， 脊椎动物的透镜，以确保相邻视网膜的正确规格、定位和图案化。突变 或者破坏晶状体内的转录网络，或者从透镜发出信号， 视网膜疾病因此，人们对确定和理解其背后的机制有着浓厚的兴趣。 由相邻的透镜引起的视网膜发育。这个应用程序的重点是使用眼睛- 果蝇触角盘作为研究诱导事件的实验系统 在眼睛的形成。眼触角盘是一个囊状结构，包含三种不同的组织。的 视网膜是由一种叫做视网膜盘的柱状上皮细胞发育而来的。在圆盘的正上方是一片 称为足周上皮的鳞状细胞。这两个层沿着它们的边缘通过 长方体细胞的条状，称为边缘（其本身来自周足上皮）。因此， 眼触角盘象一个封闭的枕套。已发表文献的证据表明， 来自足周上皮的信号传导对于诱导命运特化、生长、模式化和细胞分化是重要的。 视网膜内的命运选择而脊椎动物的透镜和苍蝇的周足上皮是非同源的 这两种组织似乎都利用共同的调控模块来诱导发育 视网膜的变化。例如，最近的研究表明，Pax 6和BMP 4/TGF β信号传导都是 视网膜发育所需的透镜和足周上皮。在本提案中，我们将讨论 许多令人兴奋的问题，去心脏了解如何发展的视网膜是由 邻近组织利用现代分子、细胞和遗传学方法，我们将开发一种最先进的 关于足周上皮如何影响眼睛发育的当代观点， 有助于头部的形成。作为这些研究的一部分，我们将继续确定转录 这些因子和信号通路在足周上皮中对于视网膜发育是重要的。这些 基因调控网络将与理解脊椎动物的透镜如何与 邻近视网膜。我们将测试Pax 6和So-Eya复合物调节生产的具体假设 TGF β和Notch信号通路的配体。从这里提出的目标，我们将获得新的 深入了解转录网络和信号通路整合的机制， 在视网膜规格和图案化期间控制感应事件。

Project Summary: Induction, the process by which one tissue signals to and influences the development of another, is a central feature of metazoan development. Some of the most famous and best studied examples of inductive interactions include the communication that takes place between the ectoderm, mesoderm, and endoderm during early embryonic development. Other examples include the signaling that leads to proper neural plate, somite, and brain development. Relevant to this proposal are the inductive cues that are sent by the vertebrate lens to ensure proper specification, positioning, and patterning of the adjacent retina. Mutations that either disrupt transcriptional networks within and signaling emanating from the lens lead to catastrophic retinal disorders. As such, there is intense interest in identifying and understanding the mechanisms underlying the induction of retinal development by the adjoining lens. This application is focused on using the eye- antennal disc of the fruit fly, Drosophila melanogaster, as an experimental system for studying inductive events during eye formation. The eye-antennal disc is a sac-like structure that contains three different tissues. The retina develops from a columnar epithelium called the disc proper. Overlying the disc proper is a sheet of squamous cells called the peripodial epithelium. These two layers are stitched together along their edges by a strip of cuboidal cells called the margin (which is itself derived from the peripodial epithelium). As such, the eye-antennal disc resembles a closed pillowcase. Evidence from the published literature indicates that signaling from the peripodial epithelium is important for inducing fate specification, growth, patterning, and cell fate choices within the retina. While the vertebrate lens and fly peripodial epithelium are non-homologous structures it appears that both tissues make use of common regulatory modules to induce developmental changes in the retina. For example, recent studies have shown that Pax6 and BMP4/TGFb signaling are both required in the lens and peripodial epithelium for retinal development. In this proposal we will address a number of exciting questions that go to the heart understanding how development of the retina is induced by neighboring tissues. Using modern molecular, cellular, and genetic methods we will develop a state-of-the-art contemporary perspective on how the peripodial epithelium influences the development of the eye and directly contributes to formation of the head. As part of these studies we will pursue the identification of transcription factors and signaling pathways that are important in the peripodial epithelium for retinal development. These gene regulatory networks will be relevant to understanding how the vertebrate lens communicates to the adjacent retina. We will test the specific hypotheses that Pax6 and the So-Eya complex regulate the production of ligands for the TGFb and Notch signaling pathways. From the aims presented here we will acquire new insights into the mechanisms by which transcriptional networks and signaling pathways are integrated to control inductive events during retinal specification and patterning.