Developmental control of C. elegans germline syncytial organization and function

胞质分裂是细胞分裂的最后一步，包括将母细胞物理分离成两个单独的子细胞。因此，它受到高度监管，它的失败可能会对生物体的发育和组织动态平衡产生戏剧性的后果。有趣的是，某些类型的细胞，如人类肝细胞，会经历受控的胞质分裂失败，形成所谓的合胞体，在这种合胞体中，多个细胞核保持相互连接，并在组织中共同发挥作用。研究细胞如何控制这种胞质分裂失败，可能会提供有用的信息，以破译正常胞质分裂过程中所需的关键调控步骤，也可以更好地理解合胞组织和器官在动物发育过程中是如何形成的。我建议使用一种特征良好的模式生物--秀丽线虫来研究这个问题。线虫的组织之一，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调节的。利用我们的方法，我们已经确定ANI-2蛋白是线虫发育过程中合胞组织和功能的关键调节因子。这项提议的目的是利用线虫中可用的强大的分子和遗传工具来确定ANI-2如何促进合胞体的形成。由于在其他多细胞生物中也发现了与ANI-2类似的蛋白质，这项工作将成为破译动物发育过程中合胞组织形成的基础。

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 tissue homeostasis. Interestingly, certain cell types, such as human liver cells, undergo controlled cytokinesis failures to form so-called syncytia, in which multiple nuclei remain 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 animal development. 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 identified the protein ANI-2 as the crucial regulator of syncytial organization and function during C, elegans development. The goal of this proposal is to use the powerful molecular and genetic tools available in C. elegans to determine how ANI-2 promotes syncytium formation. As proteins that are similar to ANI-2 are also found in other multicellular organisms, this work will serve as foundation to decipher how syncytial tissues form during animal development.