The role of cell interactions in shaping development

项目摘要 细胞之间的相互作用指导胚胎发育的许多方面。我们研究的长期目标是 该计划旨在了解细胞相互作用如何决定发育细胞的形状，组织和功能， 组织和器官利用C.线虫作为体内模型，其中遗传分析、活体成像和细胞生物学 可以结合起来，我们已经开发了几个简单的实验系统，以研究细胞相互作用 调节保守的形态发生事件。本提案的具体目标是使用这些模型系统 填补了理解细胞如何发展极性、小管如何形成以及小生境细胞如何形成的关键空白。 相互作用调节生殖细胞生物学。 在一个项目中，我们正在研究细胞接触如何诱导顶基极性。该项目涉及 两个突出的问题-细胞接触如何诱导PAR蛋白质不对称，使细胞， PAR蛋白质如何阐述其他细胞内的不对称性。我们之前发现E-钙粘蛋白信号 通过募集RhoGAP PAC-1来诱导极性，从而触发PAR蛋白质的不对称性。我们将扩展 这些发现揭示了连接PAC-1和E-钙粘蛋白胞质尾区的新分子链， 确定有助于极化的其他信号通路，并通过研究PAR如何 蛋白aPKC诱导上皮连接的形成。 在第二个项目中，我们正在研究小管是如何发展的。小管如毛细血管可以 当囊泡靶向侵入的顶端结构域时，在细胞的细胞质中形成。目前还不清楚 囊泡靶向该位点以形成胞内管。我们正在解决这个问题， 排泄细胞如何形成胞内管。我们发现PAR蛋白定位于外囊泡- 拴系复合物直接囊泡融合事件的入侵顶端域，并将扩展这些发现 通过研究PAR蛋白如何募集外囊以及如何指定管形成的初始位点。 在最后一个项目中，我们将确定小生境细胞的相互作用如何影响生殖细胞的发育。利基 细胞围绕生殖细胞和干细胞包裹膜延伸，但这些相互作用的意义是， 不太了解。我们发现原始生殖细胞（PGCs）延伸出大的突起， 并被肠细胞吞噬，消除了大部分PGC线粒体。我们将确定 PGC叶同类相食，测试假设，它有助于确保生殖细胞线粒体的健康。 总之，我们的研究结果将揭示细胞相互作用如何指导关键发育的新的基本见解。 事件，为理解细胞相互作用在人类发育中的作用提供了基础 和疾病

PROJECT SUMMARY Interactions between cells direct many aspects of embryonic development. The long-term goal of our research program is to learn how cell interactions determine the shape, organization, and function of developing cells, tissues, and organs. Using C. elegans as an in vivo model where genetic analysis, live imaging and cell biology can be combined, we have developed several simple experimental systems to investigate how cell interactions regulate conserved morphogenetic events. The specific goals of this proposal are to use these model systems to fill key gaps in understanding how cells develop polarity, how small tubes form, and how niche cell interactions regulate germ cell biology. In one project, we are investigating how cell contact induces apicobasal polarity. This project addresses two outstanding questions – how cell contacts induce the PAR protein asymmetries that polarize cells, and how PAR proteins elaborate other intracellular asymmetries. We previously discovered that E-cadherin signals to induce polarity by recruiting the RhoGAP PAC-1, which triggers PAR protein asymmetries. We will extend these findings by uncovering new molecular links connecting PAC-1 to the E-cadherin cytoplasmic tail, by identifying additional signaling pathways that contribute to polarization, and by investigating how the PAR protein aPKC induces the formation of epithelial junctions. In a second project, we are investigating how small tubes develop. Small tubes such as capillaries can form in the cytoplasm of a cell when vesicles are targeted to an invading apical domain. It is unclear how vesicles are targeted to this site to form intracellular tubes. We are addressing this question by determining how the excretory cell forms an intracellular tube. We found that PAR proteins localize the exocyst vesicle- tethering complex to direct vesicle fusion events to the invading apical domain, and will extend these findings by investigating how PAR proteins recruit the exocyst and how the initial site for tube formation is specified. In a final project, we are determining how niche cell interactions influence germ cell development. Niche cells wrap membrane extensions around germ cells and stem cells but the significance of these interactions is poorly understood. We discovered that primordial germ cells (PGCs) extend large protrusions that are wrapped and cannibalized by intestinal cells, eliminating most PGC mitochondria. We will determine the importance of PGC lobe cannibalism, testing the hypothesis that it helps ensure the health of germline mitochondria. Together, our findings will reveal new, basic insights into how cell interactions guide critical developmental events, providing a foundation for understanding the contribution of cell interactions in human development and disease.