Divide and rule: cell mixing induced by winner cells is required for loser cell elimination during cell competition. Romain V. Levayer, Eduardo Moreno. IZB institute für Zellbiologie, University of Bern, Bern, Bern, Switzerland.

   Cell competition is the mechanism by which suboptimal cell are removed from a growing tissue through apoptosis. The molecular mechanism driving the recognition of surviving cells (winners) and the cell that will die (losers) has become an intensive field of research in the past years. An increasing number of pathways modulating cell fitness and driving cell competition has been characterized in Drosophila, yet we still know very little regarding the core downstream events leading to cell elimination. Several observations in vivo and in cell cultures have shown the requirement of close contact between loser and winner cells in order to drive loser cell elimination. For instance, apoptotic cells are preferentially localized at the boundary of loser clones, and loser cell elimination is more efficient when surrounded by multiple winner cells. Yet, we still lack clear evidences showing that direct physical contact between loser and winner cells is required to drive loser elimination. Other early observations also remained unexplained so far, including: 1.The absence of competition across compartment boundary, 2.The fragmentation of loser clones. Here, we propose that loser cell elimination is controlled by the surface of contact shared with winner cells. The winner/loser surface of contact is actively increased during cell competition by the activation of loser/winner cell mixing, which is induced upstream of apoptosis. This model would explain the restrictive effect of compartment on cell competition (by preventing cell mixing) and the appearance of fragmented clones during cell competition. We will present evidences supporting this model based on : 1. Systematic quantification of clone shape in the wing disc during cell competition and in absence of apoptosis, 2. Live imaging of competition performed in the pupal notum, 3.Effect of cell mixing regulators on cell competition.