Collective effects in epithelial cell death and cell extrusion

Villars, Alexis; Levayer, Romain

doi:10.1016/j.gde.2021.09.004

Cited by 20 publications

(14 citation statements)

References 49 publications

(54 reference statements)

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“…Various types of aberrant cells can be extruded from epithelial layers, including damaged, dysfunctional, transformed, infected, aged, and dead cells. [1][2][3][4]68,69 Previous studies have demonstrated that the extrusion/removal of aberrant cells is required for proper embryonic development and also prevents ageing and tissue degeneration in the adult. 68,[70][71][72] Thus, the dysregulation of cell extrusion processes would potentially cause a variety of pathological conditions or disorders by accumulating abnormal or harmful cells within epithelial tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, cell extrusion is one of the most crucial processes by which aberrant or dysfunctional cells are actively eliminated from epithelial layers to maintain a healthy, homogenous cellular society. [1][2][3][4][5] There are two major types of cell extrusion: cell competition-mediated extrusion and apoptotic extrusion; both phenomena are evolutionarily conserved, at least partly, from flies to mammals. Cell competition is a process through which cells with different properties compete with each other for survival and space; aberrant or dysfunctional cells often become loser cells and are eventually eliminated from tissues, whereas the surrounding normal cells become winner cells that proliferate and fill the vacant spaces.…”

Section: Introductionmentioning

confidence: 99%

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Extracellular ATP facilitates cell extrusion from epithelial layers mediated by cell competition or apoptosis

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Extracellular ATP facilitates cell extrusion from epithelial layers mediated by cell competition or apoptosis

et al. 2022

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“…Cell internalization is a common event during gastrulation in metazoan embryos, as cells destined for the embryo’s interior detach their apical surfaces from the embryo’s exterior [2–5]. Given the apical-to-basal axis of such movements during C. elegans gastrulation, internalization also bears similarities to other basal extrusion events, often triggered by apoptosis or cell crowding in a variety of epithelia (reviewed in [74–76]). In all these cases, however, relatively little attention has been paid to how the cells that remain on the surface seal breaches on the embryonic exterior left behind by internalizing cells.…”

Section: Discussionmentioning

confidence: 99%

SRGP-1/srGAP and AFD-1/Afadin stabilize HMP-1/α-Catenin at rosettes to seal internalization sites following gastrulation inC. elegans

Serre¹,

Slabodnick

Goldstein

et al. 2022

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A hallmark of gastrulation is the establishment of germ layers by internalization of cells initially on the exterior. In C. elegans the end of gastrulation is marked by the closure of the ventral cleft, a structure formed as cells internalize during gastrulation, and the subsequent rearrangement of adjacent neuroblasts that remain on the surface. We found that a nonsense allele of srgp-1/srGAP leads to 10-15% cleft closure failure. Deletion of the SRGP-1 C-terminal domain led to a comparable rate of cleft closure failure, whereas deletion of the N-terminal F-BAR region resulted in milder defects. Loss of the SRGP-1 C-terminus or F-BAR domain results in defects in rosette formation and defective clustering of HMP-1/α-catenin in surface cells during cleft closure. A mutant form of HMP-1 with an open M domain can suppress cleft closure defects in srgp-1 mutant backgrounds, suggesting that this mutation acts as a gain-of-function allele. Since SRGP-1 binding to HMP-1 is not favored in this case, we sought another HMP-1 interactor that might be recruited when HMP-1 is constitutively open. A good candidate is AFD-1/Afadin, which genetically interacts with cadherin-based adhesion later during embryonic elongation. AFD-1 is prominently expressed at the vertex of neuroblast rosettes in wildtype, and depletion of AFD-1/Afadin increases cleft closure defects in srgp-1 and hmp-1R551/554A backgrounds. We propose that SRGP-1 promotes nascent junction formation in rosettes; as junctions mature and sustain higher levels of tension, the M domain of HMP-1 opens, allowing maturing junctions to transition from recruitment of SRGP-1 to AFD-1. Our work identifies new roles for α-catenin interactors during a process crucial to metazoan development.

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“…A similar transient protection was characterized in MCF10A cells and in HeLa cells [ 120 ]. These works and others [ 121 ] highlight the essential collective effects at play for the regulation of apoptosis in epithelia and the self-organized properties emerging from the integration of multiple spatial feedbacks. Levayer team is currently dissecting the contribution of these various feedbacks (positive and negative) to build a more predictive framework of apoptosis regulation at the tissue level.…”

Section: Team Workmentioning

confidence: 96%

Keeping Cell Death Alive: An Introduction into the French Cell Death Research Network

et al. 2022

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Since the Nobel Prize award more than twenty years ago for discovering the core apoptotic pathway in C. elegans, apoptosis and various other forms of regulated cell death have been thoroughly characterized by researchers around the world. Although many aspects of regulated cell death still remain to be elucidated in specific cell subtypes and disease conditions, many predicted that research into cell death was inexorably reaching a plateau. However, this was not the case since the last decade saw a multitude of cell death modalities being described, while harnessing their therapeutic potential reached clinical use in certain cases. In line with keeping research into cell death alive, francophone researchers from several institutions in France and Belgium established the French Cell Death Research Network (FCDRN). The research conducted by FCDRN is at the leading edge of emerging topics such as non-apoptotic functions of apoptotic effectors, paracrine effects of cell death, novel canonical and non-canonical mechanisms to induce apoptosis in cell death-resistant cancer cells or regulated forms of necrosis and the associated immunogenic response. Collectively, these various lines of research all emerged from the study of apoptosis and in the next few years will increase the mechanistic knowledge into regulated cell death and how to harness it for therapy.

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Collective effects in epithelial cell death and cell extrusion

Cited by 20 publications

References 49 publications

Extracellular ATP facilitates cell extrusion from epithelial layers mediated by cell competition or apoptosis

Extracellular ATP facilitates cell extrusion from epithelial layers mediated by cell competition or apoptosis

SRGP-1/srGAP and AFD-1/Afadin stabilize HMP-1/α-Catenin at rosettes to seal internalization sites following gastrulation inC. elegans

Keeping Cell Death Alive: An Introduction into the French Cell Death Research Network

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