Non-apical mitoses contribute to cell delamination during mouse gastrulation

Despin-Guitard, Evangéline; Rosa, Viviane S.; Plunder, Steffen; Mathiah, Navrita; Van Schoor, Kristof; Nehme, Eliana; Merino-Aceituno, Sara; Egea, Joaquim; Shahbazi, Marta N.; Theveneau, Eric; Migeotte, Isabelle

doi:10.1038/s41467-024-51638-6

Nat Commun

2024

DOI: 10.1038/s41467-024-51638-6

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Non-apical mitoses contribute to cell delamination during mouse gastrulation

Evangéline Despin-Guitard,

Viviane S. Rosa,

Steffen Plunder

et al.

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2024

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Cited by 2 publications

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The directionality of collective cell delamination is governed by tissue architecture and cell adhesion in aDrosophilacarcinoma model

Mira-Osuna,

Plunder,

Theveneau

et al. 2024

Preprint

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Carcinomas originate in epithelia and are the most frequent type of cancers. Tumor progression starts with the collective delamination of live tumors out of the epithelium, and requires modulation of cell adhesion. Yet, it remains elusive exactly how remodeling of epithelial cell-cell and cell-extracellular matrix contacts contribute to metastasis onset and delamination directionality. We used Drosophila melanogaster larval eye disc to study cooperative oncogenesis and determine the contribution of bi- and tricellular septate junction (SJ) components to tumor progression in flat and pseudostratified epithelia. We reveal that loss-of-function of septate junction components alone can promote cell death whereas synergic interaction with oncogenic Ras triggers the collective delamination of living tumorigenic cells. Spatiotemporal analyses reveal apical and basal delamination processes differ in terms of cell identity, cell polarity and remodeling of cell-cell and cell-ECM contacts. Using a combination of in vivo and in silico approaches, we report that SJ-depleted RasV12 tumors in pseudostratified epithelia trigger tissue folding or basal collective delamination regardless of the order in which cell contacts are remodeled. In striking contrast, SJ-depleted RasV12 tumors formed in flat, squamous epithelia, first undergo apical constriction and acquire a dome-like shape. Tumors are enriched in adhesion molecules and form an apical neck at the interface of contact between mutant cells and wild-type neighbors. Concomitant to cytoskeleton remodeling, tumors emit apical protrusions in the lumen and progressively delaminate through the apical neck while remaining cohesive. Our study reveals that tissue architecture and changes in cell adhesion drive the directionality of collective delamination of neoplastic tumors out of an epithelium.

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The directionality of collective cell delamination is governed by tissue architecture and cell adhesion in aDrosophilacarcinoma model

Mira-Osuna,

Plunder,

Theveneau

et al. 2024

Preprint

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Determinants of Antibody Levels and Protection against Omicron BQ.1/XBB Breakthrough Infection

Pérez,

Ramírez-Morros,

Jimenez

et al. 2024

Preprint

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The ongoing evolution of SARS-CoV-2, particularly through the emergence of new variants, continues to challenge our understanding of immune protection. While antibody levels correlate with protection against earlier variants like Alpha and Delta, their relationship with Omicron sub-variants remains unclear. To investigate the role of antibody levels and neutralizing activity in preventing breakthrough infections, we analyzed longitudinal SARS-CoV-2 humoral responses and neutralizing activity against the ancestral virus and major emerging variants in a well-characterized cohort of healthcare workers in Spain (N = 405). We found that antibody levels and neutralization titers are key indicators of protection against SARS-CoV-2, including the BQ.1 and XBB Omicron variants. Higher IgG and IgA levels were associated with protection over three 6-month follow-up periods sequentially dominated by BA.1, BA.2, BA.5, BQ.1, and XBB Omicron sub-variants, although the strength of the association between antibody levels and protection declined over time. Our findings demonstrate that binding antibody levels and neutralizing responses are a valid correlate of protection against more evasive BQ.1 and XBB Omicron variants, although the strength of this association declined over time. Additionally, our results underscore the importance of continuous monitoring and updating vaccination strategies to maintain effective protection against emerging SARS-CoV-2 variants.

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Non-apical mitoses contribute to cell delamination during mouse gastrulation

Cited by 2 publications

References 53 publications

The directionality of collective cell delamination is governed by tissue architecture and cell adhesion in aDrosophilacarcinoma model

The directionality of collective cell delamination is governed by tissue architecture and cell adhesion in aDrosophilacarcinoma model

Determinants of Antibody Levels and Protection against Omicron BQ.1/XBB Breakthrough Infection

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