Does ribosomal protein haploinsufficiency induce cell competition in mammalian epithelia?

Cell competition is a mechanism in which cells can be eliminated by neighboring cells with higher cellular fitness. Cell competition was discovered in Drosophila where heterozygosity for Ribosomal protein (Rp) gene mutations leads to elimination by cell competition with wild type cells. Rp gene haploinsufficiency is a common feature of aneuploid cells, and in Drosophila is largely responsible for the elimination of sporadic aneuploid cells. In mammals, Rp gene haploinsufficiency activates p53 through the nucleolar stress pathway. Cells with higher relative p53 activity are eliminated from mammalian epithelia, and p53 is also required for the selective removal of aneuploid cells from embryos. It has yet to be determined whether Rp gene haploinsufficiency leads to cell competition in mammals, how this depends on p53, and whether this contributes to aneuploid cell surveillance or tumor suppression. It is also not certain how Rp gene haploinsufficiency affects cells, other than activating the nucleolar stress pathway. We seek, using Crispr-based modification, to investigate the cellular effects of Rp gene haploinsufficiency, and to use epithelioid culture of mouse esophageal epithelium to measure cell competition in mosaic epithelia. We expect to gain insight into the contribution of Rp gene haploinsufficiency to tumor development and or cell competition to tumor suppression.