CONSTRUCTING A HIGH-RESOLUTION GENE REGULATORY NETWORK OF EMT

项目总结/摘要 上皮细胞向间质细胞转化（EMT）是许多发育过程中的重要程序。 包括原肠胚形成、神经嵴形成和肌生成的过程。急救队是一个 形态发生事件，因此，是由基因组作为一个基因发挥作用， 监管网络（GRN）。通过最近在许多物种上的进展，我们已经开始 了解调控EMT的基因调控网络。然而，我们仍然缺乏信息 这些网络是如何运作的这部分是由于GRN的缓慢性质 构建，其中主要瓶颈是鉴定顺式调节元件。我们 我建议克服这些限制，并应用新的高通量方法， 构建首个高分辨率的EMT基因调控网络。海胆胚胎 代表了一个独特的机会，以获得这样的基因调控网络的EMT。EMT的 早期海胆胚胎中的间充质细胞是可预测的，同步的，并且发生在 透明胚此外，描述胚层特化的基因调控网络 已经在海胆中得到了很好的证实。我们建议在这一知识基础上， 在高通量网络构建中应用新方法来推导高分辨率基因 EMT监管网络。这一目标将作为两个具体目标来实现。第一个目标，我们 评估已经使用共表达网络分析识别的新节点。的 第二个目的是利用顺式调节元件的高通量鉴定来鉴定 急救队的网络线路。这些目标利用了先进的EMT知识， 海胆的胚胎基因调控网络。

PROJECT SUMMARY/ ABSTRACT An Epithelial to mesenchymal transition (EMT) is an essential program in many developmental processes including gastrulation, neural crest formation, and myogenesis. EMT is a complex morphogenetic event and, as such, is governed by groups of genes functioning as a gene regulatory network (GRN). Through recent advances in many species we have begun to understand the gene regulatory networks that regulate EMT. However, we still lack information about how these networks function in detail. This is due in part to the slow nature of GRN construction in which a major bottleneck is the identification of cis-regulatory elements. We propose to overcome these limitations and apply novel high throughput methods to construct the first high-resolution gene regulatory network of EMT. The sea urchin embryo represents a unique opportunity to derive such a gene regulatory network of EMT. The EMT of mesenchymal cells in the early sea urchin embryo is predictable, synchronous, and occurs in a transparent embryo. Furthermore, gene regulatory networks describing germ layer specification have been well established in the sea urchin. We propose to build on this knowledgebase and apply new methods in high-throughput network construction to derive a high-resolution gene regulatory network of EMT. This goal will be pursued as two specific aims. In the first aim, we evaluate novel nodes that have been identified using co-expression network analysis. The second aim seeks to use high throughput identification of cis-regulatory elements to identify the EMT network wiring. These aims capitalize on the advanced state of knowledge of EMT and embryonic gene regulatory networks of sea urchin.