C. elegans gastrulation: A model for understanding apical constriction mechanisms

顶端收缩是细胞形状的改变，它驱动关键的形态发生事件，包括原肠形成 不同动物的分支形态发生和脊椎动物的神经管形成。虽然是顶端的 收缩早在一个多世纪前就被认识到了，关于根尖机制的基本问题 紧缩仍未得到回应。这个实验室的研究重点是了解细胞是如何完成 这种形状上的根本变化。人们正在研究尖端收缩，以揭示动物是如何 形成，并有助于基础科学的基础，导致改善诊断和预防 神经管缺陷。这项提案将支持一系列项目，以回答分子是如何 顶端收缩产生并传递改变细胞形状的力，是什么触发了细胞的改变 形状，发育模式机制如何部署具有必要空间的细胞生物学角色 和时间精确度，并识别和理解对 顶端收缩。该实验室开发了几项关键的技术创新来解决关键障碍 在这一领域取得进展，拟议的项目建立在实验室解剖细胞生物学的实力基础上 更一般的发展机制。根尖狭窄与部分主要根尖狭窄相交的研究 细胞和发育生物学的主题，包括细胞极化、运动活动的控制和动态 力量的控制，在一个复杂的活体环境中。拟议的项目寻求结合在一个单一的模式中 系统化对不同模型系统有价值的工具，加上实验室开发的新工具，以 为解开与关键问题相关的机制做出独特和持续的贡献 形态发生事件。

Apical constriction is a change in cell shape that drives critical morphogenetic events, including gastrulation and branching morphogenesis in diverse animals and neural tube formation in vertebrates. Although apical constriction was recognized more than a century ago, fundamental questions about mechanisms of apical constriction remain unanswered. Research in this laboratory focuses on understanding how cells accomplish this fundamental change in shape. Apical constriction is being studied to uncover insights into how animals are shaped, and to contribute to a foundation of basic science leading to improved diagnosis and prevention of neural tube defects. This proposal will support a series of projects to answer how the molecules that contribute to apical constriction generate and transmit the forces that change cell shapes, what triggers changes in cell shape, how developmental patterning mechanisms deploy cell biological players with the necessary spatial and temporal precision, and to identify and understand novel mechanisms that make important contributions to apical constriction. The laboratory has developed several key technical innovations to address critical barriers to progress in this field, and the proposed projects build on the lab's strength in dissecting cell biological mechanisms of development more generally. Study of apical constriction intersects with some of the major themes in cell and developmental biology including cell polarization, control of motor activity, and dynamic control of forces, in a complex in vivo context. The proposed projects seek to combine in a single model system the tools that are valuable to different model systems, plus the new tools that the lab has developed, to produce unique and sustained contributions to unraveling mechanisms that are relevant to critical morphogenetic events.