Spatial and Temporal Regulation of Cytokinesis in the Early Embryo

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Intellectual Merit The generation of new daughter cells from preexisting cells is a fundamental property of life, and proper development and survival necessitates that cells execute mitosis and cytokinesis with high fidelity. In animal cells, cytokinesis occurs through the action of an actomyosin contractile ring, whose position is dictated by microtubules of the mitotic apparatus. While major inroads have been made towards identifying the constituents of the contractile ring, cytokinesis remains the only phase of the cell cycle where a unifying model has yet to be distilled from the plethora of approaches and model systems employed over the last century. This project seeks to examine how models proposed for spatiotemporal regulation of cytokinesis in somatic cells apply to the early embryo, where the large cell size and rapid division cycles pose challenges not faced by cells later in development. Questions to be addressed include how the chromosome passenger complex, which translocates from the centromere to the cell equator during anaphase, contributes to cytokinesis in cells where chromosomes are dispensable for cleavage plane determination. Additionally, the project will examine how microtubules contribute to cleavage plane determination by actively suppressing contractility at the polar regions of the cell. Lastly, the project will examine how the sequence of events leading to cytokinesis are coupled to the machinery of the cell cycle. These studies will be performed on sea urchin eggs and early embryos, whose optical clarity, amenability to physical and molecular manipulation, and sequenced genome afford the ability to ask unique questions regarding the spatial and temporal regulation of cytokinesis. The planned lines of experimentation will merge classical manipulations of cellular geometry with advanced imaging, molecular- and chemical biology. Together, these studies will make significant inroads into reconciling how mechanisms directing the spatial-and temporal regulation of contractile ring assembly defined in somatic cells work in larger, embryonic cells. Broader Impact The project will increase diversity of scientists in the cellular and developmental biosciences. New Mexico State University is a minority-serving institution, and the training of underrepresented minority- and first generation college students is a fundamental part of all activities in the PI's laboratory. Minority undergraduate- and graduate trainees, including visiting scientists from tribal colleges in New Mexico, will participate in all aims of the project. To recruit participants from tribal colleges, both the PI and students will make presentations at two year- and tribal colleges to generate interest in the study and interested participants will be invited to join the research team as summer trainees or as undergraduate students enrolled at New Mexico State University. Results from the study will be shared and broadly disseminated. Images and timelapse sequences generated by the research will be integrated with the educational mission of the PI, and in-class activities utilizing the sequences will be disseminated through peer-reviewed educational web portals.