Developmental control of C. elegans germline syncytial organization and function

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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.