View Program - 63rd Annual Drosophila Research Conference

Elimination of aberrantly specified cells is vital for development and the prevention of tumour formation. While our cells carry the same genetic information, only a subset of genes are expressed in a certain cell type, determining its fate. Normal organ development heavily relies on the maintenance of correct gene expression patterns in the different cell types within it. Genetic or epigenetic mutations may cause mis-expression of fate-determining factors in cells, disrupting proper patterning and compromising organ function. It is therefore important for a mechanism to be in place to detect and remove those harmful cells. Importantly, the same strategy may be accountable for recognizing and eliminating early cancer cells with incorrect fates. However, little is known about the responsible molecular players. To elucidate this, we induced aberrantly specified patches of cells by modifying the levels of the transcription factor Apterous in Drosophila. This was done by mis-expressing its negative regulator dLMO. Apterous is expressed in the dorsal compartment of the imaginal wing disc, where it defines dorsal fate. We have since undergone 3 screens. First, we identified genes which are differentially expressed in the context of mis-specified cell elimination using RNA-seq. Then, we tested their involvement in the process with two RNAi verification screens, where we observed any potential changes in adult fly wings and larval wing discs. We reasoned that if a gene is required for aberrant clone elimination, then its downregulation would rescue those clones, leading to wing defects. In this way, we identified a set of genes that are likely involved in the process of mis-specified cell elimination.

Molecular players of mis-specified cell elimination during development