PhD Exit Seminar – Gayaanan Jeyanathan (Tepass Lab)

Epithelia are the predominant tissue type of the animal body and form major components of most organs. As with all tissues, the formation of epithelia during development and their stem cell-based renewal requires cell division. This presents a problem as division dividing epithelial cells transiently lose apical-basal polarity, which could compromise epithelial integrity How epithelial cells respond to challenges arising from cell division is not understood. To better understand the mechanisms of epithelial polarization and the impact of cell division in epithelial integrity, I have carried out a screen to identify novel epithelial polarity determinants and evaluated the relationship between cell division and epithelial cell polarity using Drosophila embryos and imaginal discs as model systems.

I carried out a genetic screen to find genes required for the normal distribution of the apical determinant Crumbs (Crb), which revealed shrub,  srpk, and the cell cycle regulator fizzy (Cdc20), as genes that are required for normal polarity.  Further analysis of fizzy mutants, which cause an arrest in metaphase in many epithelial cells confirmed the transient loss in epithelial cell polarity during cell division, leading to an in-depth analysis of the impact of cell division on epithelial cell polarity. Reducing cell division suppressed the mutant phenotypes of polarity genes arguing that cell division significantly challenges epithelial polarity leading to a higher requirement for the function of polarity regulators.  I then investigated epithelia where loss of polarity proteins such as Crb have no adverse consequences in a wildtype background. I found that accelerating cell division in such epithelia caused a loss of polarity and neoplastic tumor growth.  Moreover, neoplastic growth is strongly enhanced when accelerated division is combined with a loss of Crb. Furthermore, neoplastic growth as well as the loss of epithelial cell polarity observed in polarity mutants can be rescued by blocking cell division.  My findings indicate that the process of cell division not only increases tumor mass but also compromises epithelial polarity to drive tumor progression.

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Join Zoom Meeting:

Friday, April 23^rd, 2021 @ 2:00pm