The cellular basis of tissue separation

Fagotto, François

doi:10.1242/dev.090332

Cited by 127 publications

(95 citation statements)

References 132 publications

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“…The segregation of tissues or of tissue compartments plays fundamental roles in the regulation of growth, patterning and morphogenesis (for a review, see Fagotto, 2014). Numerous tumor suppressors and proto-oncogenes share the common feature of promoting cell segregation apparent by the rounding of somatic clones upon their loss or gain of functions, respectively (Adler et al, 1998;Johnston et al, 1999;Edgar, 2000, 2002;Garoia et al, 2000;Baena-Lopez et al, 2005;Mao et al, 2006Mao et al, , 2011Worley et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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Tumor suppressors and proto-oncogenes play crucial roles in tissue proliferation. Furthermore, de-regulation 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 the shape of somatic clones correlate with defects in proliferation, cell affinity, cell-cell adhesion, oriented cell division and cortical contractility. Combining genetics, liveimaging, laser ablation and computer simulations, we aim to analyze whether distinct or similar mechanisms can account for the common role of tumor suppressors and proto-oncogenes in cell-cell contact regulation. In Drosophila epithelia, the tumor suppressors Fat (Ft) and Dachsous (Ds) regulate cell proliferation, tissue morphogenesis, planar cell polarity and junction tension. By analyzing the evolution over time of ft mutant cells and clones, we show that ft clones reduce their cell-cell contacts with the surrounding wt tissue in the absence of concomitant cell divisions and overproliferation. This contact reduction depends on opposed changes of junction tensions in the clone bulk and its boundary with neighboring wt tissue. More generally, either clone bulk or boundary junction tension 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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…Moreover, the extent to which sorting takes part in embryogenesis, not only to actuate cell motion but also to potentially aid differentiation and cell fate specification, is largely unknown (Fagotto, 2014).…”

Section: The Role Of Adhesive Forcesmentioning

confidence: 99%

Embryoids, organoids and gastruloids: new approaches to understanding embryogenesis

2017

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Cells have an intrinsic ability to self-assemble and self-organize into complex and functional tissues and organs. By taking advantage of this ability, embryoids, organoids and gastruloids have recently been generated in vitro, providing a unique opportunity to explore complex embryological events in a detailed and highly quantitative manner. Here, we examine how such approaches are being used to answer fundamental questions in embryology, such as how cells selforganize and assemble, how the embryo breaks symmetry, and what controls timing and size in development. We also highlight how further improvements to these exciting technologies, based on the development of quantitative platforms to precisely follow and measure subcellular and molecular events, are paving the way for a more complete understanding of the complex events that help build the human embryo.

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“…The separation of two cell populations can be viewed as being based on low adhesion across the boundary, but increased actomyosin density and cytoskeletal tension at the boundary have also been implicated, for example at compartment boundaries in Drosophila (Dahmann et al, 2011;Fagotto, 2014). The concept of adhesion strength presents both mechanisms as two aspects of the same process -cortical tension increases at the boundary as adhesion is reduced, and vice versa.…”

Section: Tissue Surface Tension As a Measure Of Adhesion Strengthmentioning

confidence: 99%

Cell adhesion strength from cortical tension – an integration of concepts

Winklbauer

2015

Journal of Cell Science

162

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Morphogenetic mechanisms such as cell movement or tissue separation depend on cell attachment and detachment processes, which involve adhesion receptors as well as the cortical cytoskeleton. The interplay between the two components is of stunning complexity. Most strikingly, the binding energy of adhesion molecules is usually too small for substantial cell-cell attachment, pointing to a main deficit in our present understanding of adhesion. In this Opinion article, I integrate recent findings and conceptual advances in the field into a coherent framework for cell adhesion. I argue that active cortical tension is best viewed as an integral part of adhesion, and propose on this basis a non-arbitrary measure of adhesion strength -the tissue surface tension of cell aggregates. This concept of adhesion integrates heterogeneous molecular inputs into a single mechanical property and simplifies the analysis of attachment-detachment processes. It draws attention to the enormous variation of adhesion strengths among tissues, whose origin and function is little understood.

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The cellular basis of tissue separation

Cited by 127 publications

References 132 publications

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

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

Embryoids, organoids and gastruloids: new approaches to understanding embryogenesis

Cell adhesion strength from cortical tension – an integration of concepts

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