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

顶端收缩是一种细胞形状的变化，它驱动着细胞生长的基本事件。 形态发生，包括许多动物的原肠胚形成和神经管的形成， 脊椎动物了解细胞收缩其顶端的机制 领域将提供深入了解动物是如何形成的，它将有助于 为人类神经管闭合缺陷的诊断和预防奠定基础。 这个项目的长期目标是了解力是如何产生的， 以时空精度传输，以在发育过程中塑造细胞和组织， 有机体C.线虫原肠胚形成作为一个模型，揭示机制， 顶端收缩依赖的形态发生。C. elegans开始于 两个内胚层前体细胞经历顶端收缩并从 在胚胎发育的26至28个细胞阶段，胚胎的表面向内部延伸。 利用C. elegans使联合收割机在一个系统中结合许多工具成为可能， 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 其中一些复杂的发育现象无法研究。这些工具 包括遗传筛选和遗传操作，亚细胞定量成像 在两个大的，可预测的位置和光学透明的细胞中的动力学， 通过激光显微手术和一些新开发的工具。该项目的具体目标 是为了剖析根尖收缩的精确机制， 将细胞顶端表面的边缘与预先存在的肌动球蛋白连接起来 收缩，以确定细胞外基质在顶端收缩的作用， 研究细胞外基质成分，有助于C。线虫原肠胚形成， 并鉴定和研究有助于上述机制的新蛋白质。 这项工作有可能建立新的和意想不到的机制， 发育细胞形状的变化对不同动物的形态发生很重要 并且与人类神经管缺陷有潜在的相关性。

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.