Asymmetric Inheritance and Post-mitotic Fate of Midbodies: A Dissertation
Authors
Chen, Chun-TingFaculty Advisor
Stephen J. Doxsey, Ph.D.Academic Program
Interdisciplinary Graduate ProgramUMass Chan Affiliations
Molecular MedicineDocument Type
Doctoral DissertationPublication Date
2011-08-09
Metadata
Show full item recordAbstract
Cytokinesis is the final chapter of cell division and its last page is abscission, the physical separation of two daughter cells. During cytokinesis of vertebrate cells, two future daughter cells are connected by an intercellular bridge within which the midbody (MB) is positioned. Since becoming the focus of intense investigations on cytokinesis completion, MB is now perceived as a complicated organelle where multiple pathways for abscission are targeted and coordinated. However, whether post-mitotic midbodies, the midbody derivatives (MBds), would be retained by either daughter cell post-abscission remains unexplored. In addition, how cells manage the fate of inherited MBds is also unclear or only sketchily proposed. Finally, whether the inherited MBds in cells may play non-cytokinetic roles is also unaddressed. In the first chapter, I review the historical and current understanding of MBs, with emphasis on their roles in cytokinesis whereas potential non-cytokinetic roles are also covered. In the second chapter, the aforementioned three questions are sequentially addressed. First, the newly-formed MBd appears to be inherited by the daughter cell with the older centrosome. Second, MBds are not only inherited but also accumulated in cancer and pluripotent stem cells, but not in normal somatic (differentiated) cells. In normal somatic cells, MBds are within membrane-bound compartments for lysosomemediated degradation via autophagosome engulfment. This partially explains why MBd-accumulation is rarely observed in these cells. In contrast to the previous model, colleagues and I showed that MBd-accumulation correlates well with the autophagosomal-lysosomal activity, but not with the proliferation rate. Finally, the experimental increase of MBd levels appears to enhance the anchorage-independent growth in cancer cells and the efficiency of reprogramming in fibroblasts. In the last chapter, I conclude our findings and discuss future directions in two aspects.DOI
10.13028/f84q-ac97Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31906Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/f84q-ac97