Modulation of junction tension by tumor-suppressors and proto-oncogenes regulates cell-cell contacts

Author:

Bosveld Floris1,Guirao Boris1,Wang Zhimin1,Rivière Mathieu12,Bonnet Isabelle13,Graner François12,Bellaïche Yohanns1

Affiliation:

1. Polarity, Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 rue d'Ulm, 75248 Paris Cedex 05, France

2. Present address: Matière et Systèmes Complexes, Université Paris Diderot, CNRS UMR 7057, 10 rue Alice Domon et Léonie Duquet, 75205 Paris Cedex 13, France

3. Present address: Laboratoire Physico-Chimie Curie, Institut Curie, CNRS UMR 168, Université Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France

Abstract

Tumor-suppressor and proto-oncogenes play critical roles in tissue proliferation. Furthermore, deregulation of their functions is deleterious to tissue architecture and can result in the sorting of somatic rounded clones minimizing their contact with surrounding wild-type (wt) cells. Defects in somatic clones shape correlate with defects in proliferation, cell affinity, cell-cell adhesion, oriented cell division and cortical elasticity. Combining genetics, live-imaging, laser ablation and computer simulations, we aim to analyze whether distinct or similar mechanisms can account for the common role of tumor-suppressor and proto-oncogenes in cell-cell contact regulation. In Drosophila epithelia, Fat (Ft) and Dachsous (Ds) tumor-suppressors regulate cell proliferation, tissue morphogenesis, planar cell polarity and junction tension. By analyzing the time evolution of ft mutant cells and clones, we show that ft clones reduce their cell-cell contact with surrounding wt tissue in the absence of concomitant cell divisions and over-proliferation. This contact reduction depends on opposite changes of junction tensions in the clone bulk and its boundary with neighboring wt tissue. More generally, either clone bulk or boundary junction tensions is modulated by the activation of Yorkie, Myc and Ras yielding similar contact reductions with wt cells. Together our data highlight mechanical roles for proto-oncogene and tumor-suppressor pathways in cell-cell interactions.

Funder

Centre National de la Recherche Scientifique

Institut national de la santé et de la recherche médicale

Institut CURIE

Association pour la Recherche sur le Cancer

Agence Nationale de la Recherche

European Research Council

LAbex

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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