Myc-induced cell mixing is required for competitive tissue invasion and destruction

BioRxiv : the Preprint Server for Biology
Eduardo MorenoBarbara Hauert

Abstract

Cell-cell intercalation is used in several developmental processes to shape the normal body plan1. There is no clear evidence that intercalation is involved in pathologies. Here, we use the proto-oncogene Myc to study a process analogous to early phase of tumour expansion: Myc-induced cell competition2-7. Cell competition is a conserved mechanism5,6,8,9 driving the elimination of slow proliferating cells (so called losers) by faster proliferating neighbours (so called winners) through apoptosis10 and is important to prevent developmental malformations and maintain tissue fitness11. Using long term live imaging of Myc-driven competition in the Drosophila pupal notum and in the wing imaginal disc, we show that the probability of elimination of loser cells correlates with the surface of contact shared with winners. As such, modifying loser/winner interface morphology can modulate the strength of competition. We further show that elimination of loser clones requires winner/loser cell mixing through cell-cell intercalation. Cell mixing is driven by differential growth and the high tension at winner-winner interfaces relative to winner-loser and loser-loser interfaces, which leads to a preferential stabilisation of winner-loser conta...Continue Reading

Related Concepts

Phosphatidylinositols
Developmental Growth Involved in Morphogenesis
Bone-Implant Interface
Body Structure
Proto-Oncogenes
Actins
Science of Morphology
NOTUM gene
Larylin Husten-Loser
Neoplasms

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