Integration of orthogonal patterning information is necessary for regulating form during Drosophila body axis elongation: Towards an understanding of how genetic fate controls embryonic shape

项目摘要 后生动物胚胎的成功发育需要一系列复杂的 细胞运动和分化事件在三个维度上进行。在……里面 果蝇--发育研究中最被理解的系统之一-- 发育的信号，称为形态发生，沿着 三种转录因子形式的前/后轴(AP)，双曲面， 纳诺斯和躯干。一种单一的主要形态因子，用于沿 背侧/腹侧(DV)轴是nf/kb转录因子背侧。一种关键的方法 胚胎必须对这些信号做出反应的方式是组织它的肌球蛋白 收缩机械以产生所需的力来为协调的 在适当的时间，细胞在适当的位置移动。在.期间 生殖带延伸，果蝇体轴伸长的过程，是一种高度 生殖带内细胞间插入行为的协调模式 组织导致身体轴长度戏剧性地延长了2倍。直到最近 负责细胞的肌动球蛋白收缩装置的组装 这一过程中的插层作用被认为仅受AP构图的控制 信号。本提案所依据的初步数据描述了 随着肌球蛋白收缩而产生的意想不到的力量梯度 细菌带组织。这表明DV轴也控制着这种调节 在细菌带中肌动球蛋白收缩机械。在这方面的实验 提案将利用新开发的全球成像模式的力量来 检验两个互不相容的假设。第一个是DV图案 系统直接调制AP构图线索。第二个是监管机构 DV图案化系统的目标是收缩机械本身。答案是 对于这些问题，考虑到图案化整合的保守性 来自正交轴的信息用于控制细胞的协调运动 后生动物，应该为哺乳动物发育提供重要的新见解 和潜在的疾病病因学。

Project Summary Successful development of metazoan embryos requires that a complex series of cell movements and differentiation events be carried out in three dimensions. In Drosophila—one of the best-understood systems for developmental studies— signals for development, called morphogens, are arranged along the anterior/posterior axis (AP) in the form of three transcription factors, Bicoid, Nanos, and Torso. A single major morphogen for signaling along the dorsal/ventral (DV) axis is the nf/Kb transcription factor Dorsal. One critical way in which the embryo must respond to these signals is by organizing its myosin contractile machinery to generate the forces needed to power the coordinated movement of sheets of cells in the proper places at the proper times. During germ band extension, the process of body axis elongation in Drosophila, a highly coordinated pattern of intercalary behavior among cells within the germ band tissue leads to a dramatic 2 fold elongation of body axis length. Until recently the assembly of the actomyosin contractile apparatus responsible for cell intercalation in this process was thought to be controlled solely by AP patterning signals. Preliminary data upon which this proposal is based describes an unexpected gradient of force caused by myosin contractility that develops along the germ band tissue. This suggests that the DV axis also controls the regulation of the actomyosin contractile machinery in the germ band. Experiments in this proposal will utilize the power of a newly developed global imaging modality to test two non-mutually exclusive hypotheses. The first is that the DV patterning system modulates AP patterning cues directly. The second is that the regulatory target of the DV patterning system is the contractile machinery itself. The answer to these questions, given conserved nature of integration of patterning information from orthogonal axes for controlling coordinated cell movement in metazoans, should provide important new insights into mammalian development and potential disease etiology.