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

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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.