CONSTRUCTING A HIGH-RESOLUTION GENE REGULATORY NETWORK OF EMT

项目摘要/摘要 上皮向间充质转化(EMT)是许多发育过程中的基本程序。 包括原肠形成、神经脊形成和肌肉发生的过程。EMT是一个复杂的问题 形态发生事件，并因此由作为一个基因起作用的基因组来控制 监管网络(GRN)。通过最近在许多物种上的进展，我们已经开始 了解调节EMT的基因调控网络。然而，我们仍然缺乏信息 关于这些网络如何运作的详细信息。这在一定程度上是由于GRN的缓慢性质造成的 其中的一个主要瓶颈是识别顺式调控元件。我们 建议克服这些限制，并将新的高吞吐量方法应用于 构建首个EMT高分辨率基因调控网络。海胆胚胎 代表了一个独特的机会来衍生这样一个EMT的基因调控网络。电子仓库的EMT 早期海胆胚胎中的间充质细胞是可预测的、同步的，并出现在 透明的胚胎。此外，描述生殖层规范的基因调控网络 已经在海胆中很好地建立了。我们建议在此知识库的基础上建立 将新方法应用于高通量网络建设，获得高分辨率基因 EMT的监管网络。这一目标将作为两个具体目标来追求。在第一个目标中，我们 使用共表达网络分析评估已经识别的新节点。这个 第二个目标是寻求使用顺式调控元件的高通量识别来识别 EMT网络布线。这些目标充分利用了EMT的先进知识和 海胆胚胎基因调控网络。

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.