Mechanisms of membrane ratcheting during cell intercalation

细胞嵌入过程中的膜棘轮机制 上皮片中的细胞在相邻细胞重排下的能力是必不可少的 到组织塑造以及修复和动态平衡机制。在果蝇中 胚胎上皮，单个细胞能够巩固细胞-细胞接触或 通过收缩垂直T1接口实现的直接邻居交换移动 以及随后的水平T3界面的分辨率。最近的升值已经 这些拓扑关系中的变化是响应于脉冲 肌动球蛋白活性；然而，细胞形状改变的机制是 在收缩期后维持的情况一直不清楚。在这里，我们将探讨 依赖于膜的细胞形状棘轮机制。我们研究了棘轮是如何 机制是由小GTP酶全球环境基金活动启动的，以及这一活动如何联系起来 质膜动力学。我们将确定PtdIns脂类在全球环境基金中的功能 补充和早期形态发生，并鉴定PtdIns的磷物种和 PtdIns定位于膜棘轮的激酶。我们将进一步确定亲属的身份 肌动球蛋白网络和内吞通路在终末期和终末期的作用 棘轮事件的合并，以及这些事件之间的协调程度 流程。最后，活跃在上皮细胞中的膜运输途径 在原肠运动过程中，将检查循环和 将确定驱动界面收缩和生长的内体途径。这个 拟议的工作将是一个高度跨学科的项目，由 物理和遗传学对实验活细胞成像数据的定量分析 对这些过程的操纵。预计结果将产生全面的 对细胞骨架力量的产生如何与靶向相结合的机械论见解 质膜重塑以驱动细胞形状和拓扑的变化。

Mechanisms of membrane ratcheting during cell intercalation The ability of cells in epithelial sheets to under neighbor cell rearrangements is essential to tissue shaping as well as repair and homeostasis mechanisms. In the Drosophila embryonic epithelium, individual cells are able to either consolidate cell-cell contacts or direct neighbor exchange movements through the contraction of vertical T1 interfaces and the subsequent resolution of horizontal T3 interfaces. A recent appreciation has been that changes in these topological relationships occur in response to pulses of actomyosin activity; however, the mechanism by which cell shape changes are maintained after contractile periods has been unclear. Here, we explore the function of a membrane-dependent cell shape ratcheting mechanism. We examine how the ratcheting mechanism is initiated by small GTPase GEF activity, and how this activity can be linked to plasma membrane dynamics. We will determine the function of PtdIns lipids in GEF recruitment and early morphogenesis, and identify the PtdIns phospho-species and PtdIns kinases that localize membrane ratcheting. We will further identify the relative roles of actomyosin networks and endocytic pathways in the termination and consolidation of ratcheting events, and the degree of coordination between these processes. Finally, the membrane trafficking pathways that are active in epithelial cells during gastrulation movements will be examined, and the function of recycling and endosomal pathways in driving interface contraction and growth will be determined. The proposed work will be a highly interdisciplinary project driven by a combination of quantitative analysis of experimental live-cell imaging data with physical and genetic manipulation of these processes. The results are expected to yield a comprehensive mechanistic insight into how cytoskeletal force generation is coupled with targeted remodeling of the plasma membrane to drive changes in cell shapes and topologies.