Loss of rer1-mediated ER-stress drives cell competition in the developing Drosophila wing epithelium
Authors: Pranab Kumar Paul; Varun Chaudhary
Affiliation: Indian Institute of Science Education and Research (IISER) Bhopal, India
Keywords: s. cell competition; g. unfolded protein response
Metazoan development is a robust, error-prone process that is tightly orchestrated by several intrinsic mechanisms. Cell competition is one such process where the defective cell is sensed and eventually eliminated from the tissue. The removal process of defective cells is crucial in the course of healthy tissue development, and several mechanisms of cell competition have been extensively studied to reveal the fact. Using Drosophila as a model, many genes have been identified which can provide both selective advantages and disadvantages to the suboptimal cells, but the sensing events caused due to the physiological changes inside an unfit cell before the initiation of elimination are not conserved and still poorly understood.
Here, using the wing imaginal disc of Drosophila, we establish that the loss of rer1, an essential regulator of ER homeostasis and Notch pathway activity in higher organisms, can trigger cell competition during the development of the polarised wing discs epithelium. In the absence of Rer1, cells are eliminated through cell death via the upregulation of Unfolded Protein Response (UPR) in ER. Moreover, the elimination of rer1 depleted tissue is blocked by overexpression of the growth arrest and DNA damage-inducible protein (Gadd34), a derepressor of global translation machinery, within the mutant tissue. Unexpectedly, we found that rer1 mutant tissue showed no significant reduction in the level of protein synthesis despite having high levels of P-eIF2α, an integrated stress reporter and repressor of protein synthesis machinery, indicating that P-eIF2α may play a role other than blocking translation machinery in the absence of Rer1. However, if the excessive ER stress or any unknown reason for increased P-eIF2α in rer1 depleted tissue to trigger the elimination of mutant cells is yet to be investigated further.