Depth and Breadth of Explanatory Power in Developmental GRNs

拟议的工作分为三大领域：福尔斯。最初的目标是延长解决基因调控网络（GRNs）控制海胆胚胎规格，原肠胚阶段，包括整个胚胎。这将需要重新解决胚胎的一个剩余的复杂结构域。在此之后，我们将建立一个预测性的数字计算模型，从受精后几个小时到30小时的整个胚胎的监管规范，包括域之间的所有相互作用，使用的方法和软件最近应用于胚胎的内中胚层的一半。第二个目标是利用 合成再工程，以确定逻辑处理功能，并回答其他问题的意义，特别是网络子电路设计中遇到的海胆endomesoderm GRN。 具体来说，我们将针对双负门电路，反馈电路，并重新部署分化基因电池。这些研究将在胚胎发育的背景下进行，而不是在孤立的“玩具”电路中进行，并将利用重组BAC的组合。第三，提出了一组合作建议，其中戴维森实验室将与麦克雷实验室共同努力，其主要目标是破译形态发生功能的控制电路，戴维森实验室将与布朗纳实验室共同努力，以帮助他们的目标，获得比较GRN分析颅神经嵴和躯干神经嵴。

The proposed work falls into three general areas. The Initial objective is to extend solved gene regulatory networks (GRNs) controlling sea urchin embryonic specification, up to gastrula stage, to encompass the whole of the embryo. This will require de novo solution for one remaining complex domain of the embryo. Following this we will build a predictive digital computational model of regulatory specification throughout the embryo from a few h after fertilization to 30h, including all interactions between domains, using the approach and software recently applied to the endomesodermal half of the embryo. A second objective is to utilize synthetic re-engineering to ascertain the logic processing functions and to answer other questions about the meaning of particular network subcircuit designs encountered in the sea urchin endomesoderm GRN. Specifically we will target double negative gate circuitry, feedback circuitry, and also redeploy differentiation gene batteries. These studies will be carried out in the context of the developing embryo, rather than in isolated "toy" circuits, and will utilize combinations of recombineered BACs. Thirdly a set of collaborative proposals is presented in which the Davidson lab will work together with the McClay lab on their major objective of deciphering the control circuitry for morphogenetic functions, and the Davidson lab will work together with the Bronner lab to aid in their objective of obtaining comparative GRN analysis between cranial and trunk neural crest.