Developmental delay ensures global tissue size robustness upon local induction of apoptosis DOI Creative Commons
Ralitza Staneva,

Gabriel Sobczyk-Moran,

Florence Levillayer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 21, 2024

Abstract The capacity of our tissues to cope with external and internal stress relies on the tight coupling between cell proliferation, growth death. This is assumed be based compensatory where local mitogenic signals mechanical inputs generated by dying cells promote neighbouring proliferation. However, proliferation was mostly studied in context massive death induction, irradiation, surgical tissue ablation or upon genetic perturbation apoptosis execution. It remains thus unclear whether same mechanism operates during physiological programmed mild induction apoptosis, especially vivo . Here, we use Drosophila prospective wing (the larval disc), study impact size pattern. We first confirmed that could recover its final compensate for apoptosis. using spatial statistics found surprisingly not associated any increase it clonal compartment Compensation driven instead a JNK dependant delay lengthening stage which required reach target size. These results suggest compensation here global response rather induction. Accordingly, while total maintained despite this fails correct reduction number, hence modulating shape proportion. Overall, opens novel perspectives regulation outlines context-dependency mechanisms.

Language: Английский

DeXtrusion: automatic recognition of epithelial cell extrusion through machine learning in vivo DOI Creative Commons
Alexis Villars, Gaëlle Letort, Léo Valon

et al.

Development, Journal Year: 2023, Volume and Issue: 150(13)

Published: June 7, 2023

ABSTRACT Accurately counting and localising cellular events from movies is an important bottleneck of high-content tissue/embryo live imaging. Here, we propose a new methodology based on deep learning that allows automatic detection their precise xyt localisation fluorescent imaging without segmentation. We focused the cell extrusion, expulsion dying cells epithelial layer, devised DeXtrusion: pipeline recurrent neural networks for extrusion/cell death in large epithelia marked with contour. The pipeline, initially trained Drosophila pupal notum E-cadherin, easily trainable, provides fast accurate extrusion predictions range conditions, can also detect other events, such as division or differentiation. It performs well tissues reasonable re-training. Our could be applied detected by microscopy help to democratise use event detections developing tissues.

Language: Английский

Citations

14
Exploring caspase-dependent non-lethal cellular processes using Drosophila DOI Creative Commons
Natsuki Shinoda, Masayuki Miura

Frontiers in Cell Death, Journal Year: 2024, Volume and Issue: 3

Published: Oct. 21, 2024

Caspases are cysteine aspartic acid proteases conserved in animals that not only execute apoptosis, but also regulate diverse cellular processes independent of which termed caspase-dependent non-lethal (CDPs). Owing to its strong genetics detect and manipulate caspase activity cells interest vivo , Drosophila melanogaster serves as an excellent model organism for analyzing CDPs. This is further supported by the fact apoptotic signaling, well CDPs their mechanisms, are, part, other animals. Here, we present a review guide researchers studying using . In this review, provide overview current understanding regulates activation available genetic tools characteristics detecting manipulating so can choose appropriate own experimental settings. We introduce identified including brief description discovery characterization processes. describe underlying molecular mechanisms several well-characterized CDPs, regulatory enable activation. Finally, use proximity labeling techniques, especially TurboID, facilitates analysis mechanisms. Because caspases various functions, no longer considered point return cell death. Understanding will advance our states living dying cells, along with intermediate states.

Language: Английский

Citations

3
Epithelial apoptosis: A back-and-forth mechanical interplay between the dying cell and its surroundings DOI

Stéphanie Arnould,

Corinne Benassayag, Tatiana Merle

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 168, P. 1 - 12

Published: Feb. 21, 2025

Language: Английский

Citations

0
Intestinal Tissue Mechanics Regulate Angiogenesis and Stem Cell Proliferation via Vascular Piezo DOI Creative Commons

J. Phillips,

Jessica Perochon,

Cai T. Johnson

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract The vasculature is a prominent component of developmental and adult tissue microenvironments. How, specific characteristics environmental states influence vascular biology function, remains largely understudied. Previously, we discovered crosstalk between the intestinal epithelium vasculature-like tracheal system fruit fly Drosophila melanogaster , which driven by reactive oxygen species (ROS) during pathogen induced-intestinal regeneration. However, chemical stress signals alone are insufficient to explain rich diversity vasculature/tissue interactions in living systems justify widely observed adaptation network physiology disease. Here, uncover reciprocal, mechanochemical interorgan communication intestine its niche, shapes epithelial adaptations drives stem cell proliferation regeneration tumour growth. Mechanistically, apoptotic cells within regenerating induce local global mechanical changes gut, results activation upregulation mechanosensitive ion channel Piezo subset gut-associated trachea. molecular program trachea through transcription factor Yorkie/YAP, leading remodelling proliferation. Furthermore, identify non-redundant role Piezo1 driving crypt inducing growth, WNT signalling activity, mouse small intestine. Our cross-species vivo study reveals previously unrecognised mechanosensory regulation tumourigenesis vascular-stem niche highlights importance studying context understand plasticity complexity tissue/vasculature organ.

Language: Английский

Citations

0
Integration of past caspase activity biases cell elimination in vivo DOI Creative Commons
T. Cumming, Alexis Villars, Anđela Davidović

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

Abstract The fine tuning of apoptosis in epithelia is essential for regulating tissue size, shape, homeostasis and the maintenance sealing properties. Regulation cell death mostly orchestrated by activation Caspases, proteases which were long thought to trigger an irreversible engagement death. However, recent data vivo vitro outline numerous non-apoptotic functions caspases as well quite ubiquitous sublethal effector during development. Yet, it remains unclear many instances what drives bifurcation between survival upon caspase activation. existence a activity threshold was generally considered underpin this binary decision, but never assessed quantitatively especially at single level. Using quantitative live imaging combined with machine learning optogenetics Drosophila pupal notum (a layer epithelium), we reveal first time large heterogeneity sensitivity cells, distinct spatial domains low or high caspases. correlative perturbative experiments, central role past exposure sensitises cells several hours. Integrating information about sufficient explain most global pattern predict level will engage apoptosis. Finally, demonstrate that subset bias elimination clonal level, thus revealing alternative mechanism physiological competition. Altogether, work reveals new regulation downstream can be developmentally regulated selection

Language: Английский

Citations

0
Forward Engineering Organ Development and Cancer Therapeutics with Optogenetics DOI
Mayesha Sahir Mim,

S Cini,

Christina Frank

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 22, 2025

Robust growth control is an essential requirement for the survival of living organisms, while its dysregulation results in diseases such as cancer. However, a significant knowledge gap exists understanding how precise organ achieved. The growing arsenal optogenetic toolkits allows precise, noninvasive cellular signaling vivo, enabling research into bioelectrical and chemical cues regulate growth. Here, we used red-light-activated channelrhodopsin, CsChrimson, to stimulate intracellular calcium dynamics wing epithelium Drosophila melanogaster , established model system investigating size control. By varying light intensity activation systematically, identified biphasic regulation final size. Illumination CsChrimson depolarizes cells stimulates spikes cytosolic concentrations, phenomenon explained by computational that incorporates inclusion both junction closure voltage-gated channel activation. This tunes downstream effectors involved apoptosis. In particular, found prolonged bright red exposure (100 lux/12 hours) increased cell death imaginal discs caused severe morphological abnormalities adult wings, with phenotypic severity dependent on stimulation parameters defined illumination period Strikingly, optimum level dim, pulsatile (5 lux, 1 minute on/off pulse train) resulted overgrown organs significantly upregulated proliferation. We also co-expressed oncogene, Ras V12 showed experimental optical simulation can be exploited morphology tumorous tissues initiate targeted remission Our findings approach provide powerful framework dissect role dynamic physiological events organogenesis offer translational insights new therapeutic strategies applications cancer regenerative medicine.

Language: Английский

Citations

0
Organogenesis: Cell death matters in size and shape regulation DOI Creative Commons
Marco Milán

Current Biology, Journal Year: 2024, Volume and Issue: 34(2), P. R62 - R64

Published: Jan. 1, 2024

Language: Английский

Citations

0
Developmental delay ensures global tissue size robustness upon local induction of apoptosis DOI Creative Commons
Ralitza Staneva,

Gabriel Sobczyk-Moran,

Florence Levillayer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 21, 2024

Abstract The capacity of our tissues to cope with external and internal stress relies on the tight coupling between cell proliferation, growth death. This is assumed be based compensatory where local mitogenic signals mechanical inputs generated by dying cells promote neighbouring proliferation. However, proliferation was mostly studied in context massive death induction, irradiation, surgical tissue ablation or upon genetic perturbation apoptosis execution. It remains thus unclear whether same mechanism operates during physiological programmed mild induction apoptosis, especially vivo . Here, we use Drosophila prospective wing (the larval disc), study impact size pattern. We first confirmed that could recover its final compensate for apoptosis. using spatial statistics found surprisingly not associated any increase it clonal compartment Compensation driven instead a JNK dependant delay lengthening stage which required reach target size. These results suggest compensation here global response rather induction. Accordingly, while total maintained despite this fails correct reduction number, hence modulating shape proportion. Overall, opens novel perspectives regulation outlines context-dependency mechanisms.

Language: Английский

Citations

0