Evolutionary modification of AGS protein contributes to micromere formation in sea urchins

在进化过程中获得一种新的发育程序被认为对地球上生命的多样性有重要贡献。这项研究解决了发育生物学中的基本问题：1）一种新的细胞类型如何在发育过程中产生，2）蛋白质的进化修饰如何改变细胞和发育程序。具体来说，这项研究将确定一种名为AGS的蛋白质的进化修饰是如何促成海胆中一种新细胞类型的形成的，这种细胞类型与其亲属（如海星）的发育程序不同。这些问题基本上适用于任何多细胞生物。因此，本研究的结果有望为细胞和发育生物学的研究领域提供信息。这项研究还将通过各种外联方案对社会产生影响。这些活动包括为当地学生和公众提供实验室图尔斯之旅，以及积极参与大学范围内的外展计划，该计划使当地高中生和布朗大学的学生通过互动课程与现实世界的应用探索科学。此外，这个项目将涉及少数民族学生在实验室，他们将从事独立的研究。通过这些活动，将不断分享科学贡献，以促进各级学生对科学的兴趣。 这项研究将集中在G蛋白信号传导激活剂（AGS）上，以确定进化修饰如何促进海胆胚胎在16细胞阶段通过不对称细胞分裂形成的微粒体的形成。AGS蛋白是存在于包括人类在内的各种生物体中的极性因子。先前的研究表明，AGS负责促进16-细胞期的不对称细胞分裂，这导致微粒体的形成，微粒体是诱导内中胚层特化的主要信号中心，因此被认为是该胚胎的组织者。这从根本上改变了发展机制，使其更加有组织。重要的是，海胆AGS的引入，而不是海星星AGS，诱导不对称的细胞分裂和组织者样细胞在海星星胚胎的形成。基于这些观察结果，该项目将测试AGS修饰如何有助于微粒细胞作为一种新的细胞类型的进化引入，从而导致目前的海胆发育计划。具体而言，AGS功能的微球形成，AGS蛋白在海胆多样化的过程中的进化转变，以及AGS蛋白修饰对创建新的细胞类型的贡献的分子机制，将使用细胞和胚胎学方法进行研究。棘皮动物胚胎的实验系统是适合于这个研究计划，因为它提供了材料的光学透明度，操作细胞的能力，以及可以分析的不平等细胞分裂的良好描述的发育后果。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

Acquisition of a novel developmental program during evolution has been proposed to have important contributions to the diversity of life on earth. This research addresses fundamental problems in developmental biology: 1) how a new cell type arises in development and 2) how the evolutionary modifications of the protein could change the cell and developmental program. Specifically, this study will identify how evolutionary modifications of a protein called AGS contributed to the formation of a new cell type in the sea urchin, which is distinct from the developmental program of its relatives, such as sea stars. These questions are fundamentally applicable to any multi-cellular organism. Therefore, outcomes of this study are expected to inform the research field of cell and developmental biology. This research will also have an impact to society through various outreach programs. Those activities include providing lab tours to local students and the public, as well as active involvement in the University-wide outreach program, which brings local high school students and Brown students to explore science through interactive lessons with real-world applications. Further, this project will involve minority students in the lab where they will engage in independent research. Through these activities there will be a continuous sharing of scientific contributions to promote an interest in science among students at many levels. This research will focus on Activator of G-protein signaling (AGS) to identify how evolutionary modifications contributed to the formation of micromeres that are formed through an asymmetric cell division at the 16-cell stage in the sea urchin embryo. AGS protein is a polarity factor present in various organisms, including humans. Previous research demonstrated that AGS is responsible for facilitating an asymmetric cell division at the 16-cell stage, which results in the formation of micromeres—a major signaling center that induces endomesodermal specification and thus considered as an organizer in this embryo. This fundamentally changes the mechanism of development by making it more organized. Importantly, introduction of sea urchin AGS, but not sea star AGS, induced asymmetric cell divisions and formation of organizer-like cells in the sea star embryo. Based on these observations, the project will test how AGS modification contributed to evolutionary introduction of micromeres as a new cell type, leading to the current developmental program of sea urchins. Specifically, molecular mechanisms of AGS function in micromere formation, evolutionary transition of AGS protein in the process of sea urchin diversification, and contribution of AGS protein modifications to creation of a new cell type, will be investigated using cell and embryological approaches. Experimental system of echinoderm embryos is suitable for this research program because it offers the optical transparency of the material, the ability to manipulate the cells, and the well-described developmental consequences of the unequal cell division that can be assayed.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.