Cytokinesis in Caenorhabditis Elegans

本项目旨在了解动物细胞分裂的基本过程 （胞质分裂）。最近发现，动物细胞胞质分裂分为两个阶段：周向卵裂沟的进入和膜在残留的细胞间桥处的最终破裂和重新密封（断裂）。调查将集中在用于执行在线虫秀丽隐杆线虫的早期发展的断裂的机制。Prevoius的研究表明，分裂过程需要有丝分裂纺锤体的中间体和卵裂沟区域的靶向胞吞作用。有人建议使用功能抑制的基因，编码组件的中间体加上细胞学检查所得的表型在体内作为一种手段，确定这些组件中的作用，执行切断的机器。我们专注于两个在断裂中起关键作用的基因，spd-1和Y18 D10 A。17.我们将确定这些基因如何与已知的断裂机制的组成部分相互作用，也将寻求其他相互作用的蛋白质，以揭示断裂中使用的遗传途径。这些研究将补充研究膜运输到该地区的细胞间桥在切断时。通过 使用与体内成像结合使用的隔室特异性探针，将确定在切割期间靶向晚期切割沟的膜的来源。使用光学显微镜的晚期细胞动力学沟的体内观察将通过使用电子显微镜的研究来补充，以可视化中间体和膜交通的细胞骨架成分之间的超微结构相互关系。 胞质分裂是一个基本的细胞过程，因此其功能障碍可能导致病理学。如果分裂失败，所产生的多极细胞的任何随后的分裂将导致无定形子细胞，其可能失去正常的生长控制并不适当地增殖。例如，已知石棉丝会干扰卵裂沟。这一机制可以解释石棉暴露的致癌作用。

This project seeks to gain an understanding of the fundamental process of animal cell cleavage (cytokinesis). It has recently become apparent that animal cell cytokinesis is executed in two phases: the ingression of a circumferential cleavage furrow and the final breaking and resealing of membrane at the residual intercellular bridge (scission). The investigations will focus on the mechanisms that are used to execute scission in the early development of the nematode Caenorhabditis elegans. Prevoius studies have shown that the process of scission requires the presence of the mid-body of the mitotic spindle and targetedocytosis in the region of the cleavage furrow. It is proposed to use functional suppression of genes that encode components of the mid-body coupled with cytological examination of the resultant phenotype in vivo as a means of identifying the role of these components in the machinery that executes scission. We are focusing on two genes that have critical roles in scission, spd-1 and Y18D10A. 17. We will determine how these genes interact with known components of the scission machinery and will also seek other interacting proteins in order to uncover the genetic pathways used in scission. These studies will be complemented by studies of membrane trafficking to the region of the intercellular bridge at the time of scission. Through the use of compartment-specific probes used in conjunction with in vivo imaging, the source of the membrane that is targeted to the late cleavage furrow during scission will be determined. The in vivo observations of the late cytokinetic furrow using the light microscope will be complemented by studies using electron microscopy in order to visualize the ultrastructural interrelationship between the cytoskeletal components of the mid-body and membrane traffic. Cytokinesis is a fundamental cellular process, and as such its malfunction could result in pathologies. If a cleavage fails, any subsequent cleavage of the resulting multipolar cell would result in anuploid daughter cells, which could lose normal growth controls and proliferate inappropriately. For example, filaments of asbestos as are known to interfere with cleavage furrows. This mechanism could explain the carcinagenetic effects of asbestos exposure.