Cytokinesis in Caenorhabditis Elegans

这个项目试图了解动物细胞分裂的基本过程。 (细胞质分裂)。最近发现，动物细胞胞质分裂分两个阶段进行：周向分裂沟的进入和在残留的细胞间桥(断裂)处膜的最终断裂和重新密封。调查将集中在线虫线虫早期发育过程中用于执行分裂的机制。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细胞吞噬作用。有人建议使用编码中间体组成部分的基因的功能抑制与体内产生的表型的细胞学检查相结合，作为确定这些组成部分在执行分裂的机制中的作用的一种手段。我们正在关注两个在分裂中起关键作用的基因，Spd-1和Y18D10A。17.我们将确定这些基因如何与分裂机制的已知组件相互作用，并将寻找其他相互作用的蛋白质，以揭示分裂中使用的遗传途径。这些研究将得到在细胞分裂时膜运输到细胞间桥区域的研究的补充。通过 使用隔室特异性探针与体内成像相结合，将确定在分裂过程中针对晚期卵裂沟的膜的来源。用光学显微镜对晚期细胞动沟的活体观察将辅之以电子显微镜的研究，以可视化中体细胞骨架成分与膜运输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，因此它的故障可能会导致病理。如果分裂失败，随后对多极细胞的任何分裂都会导致子代细胞分裂，从而失去正常的生长控制并不适当地增殖。例如，众所周知，石棉细丝会干扰乳沟.这一机制可以解释石棉暴露的致癌效应。

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.