Induction of retinal development by the peripodial epithelium in Drosophila

项目摘要：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展的中心特征。一些最著名和研究最深入的例子 诱导相互作用包括发生在外胚层、中胚层和 胚胎发育早期的内胚层。其他例子包括导致适当的信号发送 神经板、体节和大脑发育。与这项提议相关的是由 脊椎动物的晶状体，以确保相邻视网膜的适当规格、位置和图案。突变 要么扰乱晶状体内部的转录网络，要么从晶状体发出信号导致灾难性的 视网膜疾病。因此，人们对确定和了解潜在的机制有着浓厚的兴趣 由邻近的晶状体引起的视网膜发育。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 在眼睛形成过程中。眼球触角盘是一个囊状结构，包含三个不同的组织。这个 视网膜由一种叫做视盘本身的柱状上皮发育而来。覆盖在光盘上的是一张 鳞状细胞称为足周上皮。这两个层是通过一个 长条状的立方细胞，称为边缘(其本身来源于足周上皮)。因此， 眼睛触角盘就像一个封闭的枕套。已出版文献中的证据表明 来自足周上皮的信号对于诱导命运规范、生长、图案化和细胞是重要的。 视网膜内的命运选择。而脊椎动物的晶状体和苍蝇的牙周上皮是不同源的 结构似乎这两个组织都利用共同的调节模块来诱导发育 视网膜的变化。例如，最近的研究表明，Pax6和BMP4/TGFb信号都是 视网膜发育所需的晶状体和足周上皮细胞。在这项提案中，我们将解决 一些令人兴奋的问题进入心脏，了解视网膜是如何由 邻近的组织。使用现代分子、细胞和遗传方法，我们将开发出一种最先进的 关于足周上皮如何直接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，我们将继续研究转录的鉴定 在视网膜发育过程中，在视网膜周围上皮中起重要作用的因素和信号通路。这些 基因调控网络将与理解脊椎动物晶状体如何与 相邻的视网膜。我们将检验Pax6和So-Eya复合体调节生产的具体假设 TGFb和Notch信号通路的配体。从这里提出的目标中，我们将获得新的 对转录网络和信号通路整合机制的洞察 控制视网膜规范和图案化过程中的感应事件。

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.