Spatial and Temporal Regulation of Cytokinesis in the Early Embryo

早期胚胎细胞分裂的时空调节

• 批准号: 0818729
• 负责人: Charles Shuster
• 金额: $ 57.97万
• 依托单位: New Mexico State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0818729&HistoricalAwards=false
• 关键词: Spatial; Temporal; Regulation; Cytokinesis; Early

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.

智力优势 从先前存在的细胞产生新的子细胞是生命的基本属性，并且适当的发育和存活需要细胞以高保真度执行有丝分裂和胞质分裂。在动物细胞中，胞质分裂通过肌动球蛋白收缩环的作用发生，其位置由有丝分裂器的微管决定。 虽然主要的进展已经朝着确定收缩环的成分，胞质分裂仍然是唯一的阶段，其中一个统一的模型还没有从过去世纪采用的方法和模型系统的过剩蒸馏。 该项目旨在研究体细胞胞质分裂时空调控模型如何应用于早期胚胎，其中大细胞大小和快速分裂周期构成了细胞在发育后期所面临的挑战。 要解决的问题包括如何染色体乘客复合体，从着丝粒易位到细胞赤道在分裂后期，有助于胞质分裂的细胞中，染色体是卵裂面确定。 此外，该项目将研究微管如何通过积极抑制细胞极区的收缩性来促进裂解平面的确定。 最后，该项目将研究导致胞质分裂的事件序列如何与细胞周期的机制相结合。这些研究将在海胆卵和早期胚胎上进行，它们的光学清晰度，对物理和分子操作的顺从性，以及测序的基因组，能够提出关于胞质分裂的空间和时间调节的独特问题。 计划中的实验路线将把细胞几何学的经典操作与先进的成像、分子和化学生物学结合起来。 总之，这些研究将在协调体细胞中定义的收缩环组装的时空调控机制如何在较大的胚胎细胞中发挥作用方面取得重大进展。 更广泛的影响 该项目将增加细胞和发育生物科学科学家的多样性。 新墨西哥州州立大学是一所为少数群体服务的机构，对代表性不足的少数群体和第一代大学生的培训是PI实验室所有活动的基本组成部分。 少数民族本科生和研究生受训人员，包括来自新墨西哥州部落学院的访问科学家，将参与该项目的所有目标。 为了从部落学院招募参与者，PI和学生将在两年制和部落学院进行演讲，以引起对研究的兴趣，感兴趣的参与者将被邀请作为暑期实习生或新墨西哥州州立大学的本科生加入研究团队。 研究结果将得到分享和广泛传播。 研究产生的图像和时间推移序列将与PI的教育使命相结合，利用序列的课堂活动将通过同行评审的教育门户网站传播。