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可以在三个维度上进行。在 果蝇是发育研究中最为人所知的系统之一， 发育的信号，称为形态发生素，沿着沿着。 前/后轴（AP）以三种转录因子的形式，Bicoid， 纳米和躯干。一个主要的形态发生蛋白，用于沿着 背/腹（DV）轴是nf/Kb转录因子Dorsal。一个关键的方式 胚胎对这些信号的反应是组织肌球蛋白 收缩机械产生所需的力量，以推动协调 细胞片在适当的时间在适当的位置移动。期间 胚带延伸是果蝇体轴伸长的过程， 生殖带内细胞间的协调的插入行为模式 组织导致体轴长度显著延长2倍。直到最近 负责细胞收缩的肌动球蛋白收缩装置的组装 在此过程中的嵌入被认为是由AP图案化单独控制的 信号.本建议所依据的初步数据描述了 肌球蛋白收缩力引起的意外梯度，肌球蛋白收缩力沿着 生殖带组织这表明DV轴也控制着调节 的肌动球蛋白收缩机制。在这方面的实验 该提案将利用新开发的全球成像模式的力量， 测试两个不相互排斥的假设。首先是DV模式 系统直接调节AP模式提示。第二，监管 DV图案化系统的目标是收缩机械本身。答案 对于这些问题，考虑到模式化整合的保守性， 用于控制协调小区移动的正交轴的信息， 后生动物，应该提供重要的新见解哺乳动物的发展 和潜在的疾病病因。

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.