Though all the cells of the same cell type in a tissue of a multicellular organism may appear interchangeable, this is not always the case. Throughout an organism’s lifespan, they will encounter many insults that lead to damage or mutation of cells, introducing heterogeneity into otherwise near homogeneous tissues. In the case deleterious heterogeneities, such as cells with decreased ability to grow, it benefits the organism to have fitness sensing mechanisms that can detect these cells and eliminate them.
Cell competition was first identified as a mechanism that eliminates slower growing cells possessing ribosomal protein mutations in mosaic tissues with normally growing cells. Since its discovery, cell competition has been found to be induced by numerous genetic differences, including instances where the wild-type cells are eliminated by faster growing cells overexpressing the growth factor Myc, termed Myc super-competition.
Though cell competition is primary viewed as a local cell-to-cell signaling event that determines fitness and eliminates less-fit cells, in this dissertation I identify a novel function of the steroid hormone ecdysone as a systemic, restrictive regulator of Myc super-competition in Drosophila. I find that Dilp8-Lgr3 signaling in the central nervous system represses ecdysone biosynthesis to systemically maintain a low-ecdysone, permissible environment for Myc super-competition.
In further work that has begun probing how the level of systemic ecdysone prevents neighboring cell populations from undergoing Myc super-competition, I have found that the level of Myc in cells interacts with ecdysone through a variety of mechanisms, including being able to upregulate Dilp8 and downregulate the ecdysone receptor complex. This work lays the foundation for further work to investigate the mechanism by which ecdysone regulates Myc super-competition.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/gt5f-3285 |
| Date | January 2024 |
| Creators | Bellah, Jeffrey Lawrence |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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