C. elegans Gastrulation: a Model for Understanding Apical Constriction Mechanisms

心尖收缩是一种细胞形状的改变，它驱动了 形态发生，包括许多动物的原肠形成和神经管的形成 脊椎动物。对细胞收缩其顶端机制的理解 领域将提供对动物是如何塑造的洞察，它将有助于 为诊断和预防人类神经管闭合缺陷奠定了基础。 这个项目的长期目标是了解力量是如何产生和 以时空精度传输以塑造发育中的细胞和组织 有机体。线虫原肠发育可作为揭示线虫原肠发育机制的模型 顶端收缩依赖的形态发生。线虫的原肠发育始于 两个内胚层前体细胞正在经历根尖收缩并从 胚胎的表面向内，处于胚胎发育的26-28个细胞阶段。 使用线虫可以将许多工具组合到一个系统中，这些工具是 在其他模型系统中有价值，包括主要用于培养细胞系统的工具 其中一些复杂的发展现象是无法研究的。这些工具 包括基因筛选和基因操作、亚细胞定量成像 在两个大的、可预测的位置和光学清晰的单元格中的动力学，力的探测 通过激光显微手术，以及一些新开发的工具。这个项目的具体目标是 是对触发心尖部收缩的精确机制进行剖析 将细胞顶端表面的边缘连接到预先存在的肌动球蛋白 收缩，以确定细胞外基质在根尖收缩中的作用 研究一种有助于线虫原肠形成的细胞外基质成分， 并鉴定和研究与上述机制有关的新蛋白质。 这项工作有可能建立新的和意想不到的机制 发育中的细胞形状变化对不同动物的形态发生很重要 可能与人类神经管缺陷有关。

Apical constriction is a cell shape change that drives fundamental events of morphogenesis, including gastrulation in many animals and neural tube formation in vertebrates. An understanding of the mechanisms by which cells shrink their apical domains will provide insights into how animals are shaped, and it will contribute to a basic foundation for the diagnosis and prevention of human neural tube closure defects. The long-term goal of this project is to understand how forces are produced and transmitted with spatiotemporal precision to shape cells and tissues in developing organisms. C. elegans gastrulation serves as a model for revealing mechanisms of apical constriction-dependent morphogenesis. Gastrulation in C. elegans begins with two endodermal precursor cells undergoing apical constriction and moving from the embryo's surface to the interior, at the 26- to 28-cell stage of embryonic development. Using C. elegans makes it possible to combine in a single system many tools that are valuable in other model systems, including tools used primarily in cultured cell systems in which some complex developmental phenomena cannot be studied. These tools include genetic screens and genetic manipulations, quantitative imaging of subcellular dynamics in two large, predictably positioned and optically clear cells, probing of forces by laser microsurgery, and some newly developed tools. The specific aims of this project are to dissect precise mechanisms by which apical constriction is triggered by connecting the edges of the cells' apical surfaces to pre-existing actomyosin contractions, to determine the role of extracellular matrix in apical constriction by studying an extracellular matrix component that contributes to C. elegans gastrulation, and to identify and study new proteins that contribute to the mechanisms studied above. The work has the potential to establish new and unexpected mechanisms for a developmental cell shape change that is important to morphogenesis in diverse animals and with potential relevance to human neural tube defects.