Bembenek Lab

New Roles for Cytokinesis in Development

Our interest in abscission, the final event that separates daughter cells during cytokinesis, began with the observation made in the Csankovszki lab that condensin I localizes to the central spindle and midbody. Our 2013 paper indicated that Aurora B regulates abscission in response to chromatin bridges by recruiting condensin I to promote bridge resolution and prevent cytokinesis failure. Other studies indicated that Aurora B regulates abscission in response to developmental cues to regulate precisely when and how daughter cells disconnect from one another at the end of cytokinesis. Aurora B localizes to a structure known as the midbody. A number of controversial studies in recent years have suggested that the midbody has functions beyond abscission in cell fate and polarization and is not simply “cellular junk” as previously thought. The midbody has also been shown to be involved in generating apical polarity in MDCK cells, because key apical markers are delivered to the midbody by Rab11 vesicle trafficking at the end of cytokinesis.

We sought to further understand potential functions of the midbody by studying cytokinesis during the development of the C. elegans embryo, which is the only organism with a complete map of the invariant embryonic cell divisions. Through a systematic characterization of several cytokinetic regulators, we have discovered reproducible patterns in furrow symmetry, midbody movement and inheritance in the early embryo. Interestingly, several tissues undergo a highly modified cytokinesis during morphogenesis. Cells in the gut, pharynx and sensilla neurons, form a midbody at a central position between each daughter cell pair. The midbody subsequently migrates to the nascent apical surface of that tissue during epithelial polarization. Unexpectedly, Aurora B kinase remains on the apical surface for an extended period after cytokinesis while other midbody proteins are internalized and degraded. Inactivation of Aurora B disrupts formation of apical structures. Therefore, Aurora B kinase may regulate cytokinetic events and functions after abscission to regulate the apical surface of the cell. 

This project is an exciting new direction for the lab and opens a novel area of investigation for future projects. Several interesting questions are: what are the fate and function of midbodies in the stereotypical embryo divisions? Do midbodies of different cells have different membrane or protein components that control their function and affects? What is the role of Aurora B at the apical surface and how is it regulated?

This work demonstrates that cells in several tissues undergoing the mesenchymal to epithelial transition are in the final stages of cytokinesis, which has important implications for understanding their behavior. Cytokinesis involves precise regulation of most cytoskeletal and membrane systems and is the transition when all the intracellular compartments return to their interphase configuration, making it an ideal time to reorganize cellular architecture. This could be an important principle used by cells to achieve specific organized states in tissues during development. It will be fascinating to determine whether specific developmental pathways control aspects of cytokinesis to achieve their functions in regulating cellular behavior and organization within tissues.