62 Oral - Cell Division and Cell Growth
Friday April 08, 9:00 AM - 9:15 AM

Authors:
Colby Schweibenz; Ken Moberg

Affiliation: Emory University

Keywords:
s. cell competition; s. other (intersection of multiple signaling pathways)

The phenomenon of cell competition ensures that the fittest cells populate developing primordia but is also postulated to underlie the phenomenon of “field cancerization,” in which cancer cells expressing ‘super-competitor’ genes eliminate slow growing neighbors and take over an epithelial tissue. Our prior work demonstrated that cells overexpressing the Drosophila protein Taiman (Tai; human NCOA3/AIB1), a transcriptional co-activator of the Ecdysone receptor (EcR), are able to kill wild type neighbors within the larval wing epithelium in a manner dependent on production of the Toll ligand Spätzle (Byun et al, 2019). Here we use the wing disc to test and confirm the reciprocal hypothesis, that cells with reduced Tai expression (Tai^low) are competitive ‘losers,’ and we use a genetic screen in the adult eye to identify candidate mechanisms required for elimination of these cells by wild type neighbors. This screen recovered ‘hits’ in the pro-apoptotic genes, head involution defective, reaper, and grim, as dominant suppressors of the loss of Tai^low cells, confirming a competitive mechanism that operates through the classic DIAP-RHG-Caspase apoptotic pathway. In addition to these validating ‘hits’, we also recovered alleles of factors involved in cell:cell signaling pathways that are thus candidates to act downstream of Tai to control competitive fate. Our studies have focused on two of these: the two Drosophila Adenomatous polyposis coli (APC) tumor suppressor homologs, Apc1 and Apc2, which are conserved elements of the Wg pathway and inhibit field cancerization in the fly midgut (Suijkerbuijk, 2016). We find that Apc1/Apc2 loss rescues elimination of Tai^low cells in both eye and wing epithelia, and couple this with evidence that Tai controls some Wg-target genes in larval wing cells. We will describe ongoing experiments to establish mechanistic links between Tai and Wg/Apc in the wing epithelium, with the goal of defining how the Tai/EcR and Wg/Apc pathways intersect to determine winner/loser status in Drosophila epithelia.