Developmental control of C. elegans germline syncytial organization and function

胞质分裂是细胞分裂的最后一步，包括母细胞物理分离成两个单独的子细胞。因此，它受到高度调控，其失败可能对生物体的发育和形成成年生物体的各种组织产生严重后果。有趣的是，某些细胞类型，如产生精子和胚珠的细胞，经历受控的胞质分裂失败，形成所谓的合胞体，其中多个核保持物理连接，并在组织中一起发挥作用。研究细胞如何控制这种胞质分裂失败可能提供有用的信息，以破译在正常胞质分裂过程中所需的关键调节步骤，而且还可以更好地了解合胞体组织和器官在动物发育过程中是如何形成的。 我建议研究这个问题，使用一个良好的模式生物，线虫秀丽隐杆线虫。C.线虫的生殖系是以合胞体的形式组织的，我们已经开发了新的方法来表征这种合胞体组织在动物发育过程中是如何被调节的。使用我们的方法，我们发现，像人类一样，单个C。线虫细胞，最终将产生精子和卵母细胞（C。秀丽线虫胚珠）胞质分裂失败。使用C.然而，我们可以看到细胞分裂，因为动物是透明的，因此我们可以使用各种方法来确定为什么它们不能进行胞质分裂。这项建议的目的是利用C. elegans来确定是什么基因使C.并评估这些事件对动物发育的影响。如C。在包括人类在内的其他多细胞生物体中也发现了秀丽隐杆线虫的基因，这项工作将为破译动物发育过程中合胞体组织是如何形成的奠定基础。

Cytokinesis is the final step of cell division and consists in the physical separation of a mother cell into two individual daughter cells. As such, it is highly regulated and its failure can have dramatic consequences on an organism's development and on the various tissues that form an adult organism. Interestingly, certain cell types, such as the cells that will give rise to sperm and ovules, undergo controlled cytokinesis failures to form so-called syncytia, in which multiple nuclei remain physically connected to one another and function together in a tissue. Studying how cells control such cytokinesis failures may provide useful information to decipher the critically regulated steps that are required during normal cytokinesis, but also to better understand how syncytial tissues and organs are formed during the development of animals. I propose to study this problem using a well-characterized model organism, the nematode Caenorhabditis elegans. One of the tissues of C. elegans, the germline, is organized as a syncytium, and we have developed novel methods to characterize how this syncytial organization is regulated during development of the animal. Using our methods, we have found that, like in humans, the single C. elegans cell that will eventually give rise to the sperm and oocytes (C. elegans ovules) fails cytokinesis. The advantage of using C. elegans however is that we can see the cells divide because the animal is transparent, and therefore we can use various approaches to determine why they fail cytokinesis. The goal of this proposal is to use the powerful molecular and genetic tools available in C. elegans to determine what are the genes that enable controlled cytokinetic failures in C. elegans and assess what are the consequences of such events on the development of the animal. As many C. elegans genes are also found in other multicellular organisms, including humans, this work will serve as foundation to decipher how syncytial tissues are built during animal development.