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PhD Transfer Seminar – Meggie Cao (Tepass Lab)

April 9, 2021 @ 12:00 pm - 12:30 pm

Interactions between polarity proteins and Yorkie-mediated tissue growth




Precise regulation of organ growth is a fundamental aspect of multicellular organisms. Pioneering studies in Drosophila melanogaster have identified the conserved Hippo-Yorkie(Yki) pathway as an essential signaling network involved in regulating epithelial tissue growth. Loss of Hippo pathway activity and the consequent activation of Yki promotes hyperplastic tissue overgrowth but does not cause the formation of malignant tumors that have lost epithelial integrity. The human counterpart of Yki, YAP, is also associated with tumor initiation, progression and poor prognosis in various cancers. The core components of the Hippo pathway are well characterized. In contrast, how the Hippo pathway is regulated through a number of upstream regulators that are linked to the epithelial organization, in particular, cell polarity and cell adhesion networks, remains an active area of research.


I plan to investigate the interactions between cell polarity and the Hippo/Yki pathway in the Drosophila larval wing imaginal disc. My first aim is to determine if the RhoGEF Cysts our lab characterized recently regulates growth by modulating Yki activity or the activity of other signaling pathways such as the JNK pathway. To date, I have found that Cysts is enriched at apical junctions throughout the wing disc and plays an essential role in maintaining epithelial integrity and cell viability during wing disc development. Loss of Cysts led to excessive epithelial folding and loss of epithelial polarity when cell death is inhibited. The loss of epithelial integrity was associated with an upregulation of JNK, Wingless, and Yki signaling. Furthermore, defects were enhanced by the loss of both Cysts and RhoGEF2, suggesting that these RhoGEFs function cooperatively. Going forward, I plan to further characterize the function of Cysts in wing discs epithelial morphogenesis and growth regulation.


My second aim addresses whether Yki target genes contribute to epithelial stability and, in turn, whether the disruption of those target genes in conjunction with Yki can promote malignant tumor progression. Our lab has recently established that hyperproliferation causes a breakdown of epithelial structure that contributes to tumor progression from hyperplastic to neoplastic growth. The question arises how tissue with active Yki that shows hyperproliferation can maintain epithelial polarity. We speculate that Yki has target genes that act to protect epithelial integrity. I plan to identify candidate Yki targets that could contribute to epithelial structure from available genetic and molecular screen data. Candidate genes will be depleted in the presence of active Yki to assess whether they are required for epithelial stability during Yki promoted hyperproliferation.


Overall, this work hopes to gain a more comprehensive understanding of the mechanisms involved in Yki activation and function, which are highly relevant for normal development and cancer progression.



Join Zoom Meeting:


Friday, April 9th, 2021 @ 12:00pm


Meeting ID: 859 5202 8560

Host: Ulrich Tepass (u.tepass@utoronto.ca)


April 9, 2021
12:00 pm - 12:30 pm