Automated counting of Drosophila imaginal disc cell nuclei

Biology Open, Год журнала: 2024, Номер 13(2)

Опубликована: Фев. 12, 2024

ABSTRACT Automated image quantification workflows have dramatically improved over the past decade, enriching analysis and enhancing ability to achieve statistical power. These analyses proved especially useful for studies in organisms such as Drosophila melanogaster, where it is relatively simple obtain high sample numbers downstream analyses. However, developing wing, an intensively utilized structure developmental biology, has eluded efficient cell counting due its highly dense cellular population. Here, we present automated capable of quantifying cells wing. Our can count total number or clones labeled with a fluorescent nuclear marker imaginal discs. Moreover, by training machine-learning algorithm developed workflow segmenting twin-spot nuclei, challenging problem requiring distinguishing heterozygous homozygous background regionally varying intensity. could potentially be applied any tissue density, they are structure-agnostic, only require label segment cells.

Язык: Английский

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Cell competition: emerging signaling and unsolved questions

FEBS Letters, Год журнала: 2024, Номер 598(4), С. 379 - 389

Опубликована: Фев. 1, 2024

Multicellular communities have an intrinsic mechanism that optimizes their structure and function via cell–cell communication. One of the driving forces for such self‐organization multicellular system is cell competition, elimination viable unfit or deleterious cells interaction. Studies in Drosophila mammals identified multiple mechanisms competition caused by different types mutations cellular changes. Intriguingly, recent studies found “losers” commonly show reduced protein synthesis. In , reduction synthesis levels loser phosphorylation translation initiation factor eIF2α a bZip transcription Xrp1. Given variety stresses converge on thus global inhibition synthesis, may be machinery fitness removing stressed cells. this review, we summarize discuss emerging signaling critical unsolved questions, as well role competition.

Язык: Английский

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DrosophilaTNF/TNFRs: At the crossroad between metabolism, immunity, and tissue homeostasis

FEBS Letters, Год журнала: 2023, Номер 597(19), С. 2416 - 2432

Опубликована: Авг. 12, 2023

Tumor necrosis factor (TNF)-α is a highly conserved proinflammatory cytokine with important functions in immunity, tissue repair, and cellular homeostasis. Due to the simplicity of Drosophila TNF-TNF receptor (TNFR) system broad genetic toolbox, fly has played pivotal role deciphering mechanisms underlying TNF-mediated physiological pathological functions. In this review, we summarize recent advances our understanding how local systemic sources Egr/TNF contribute its antitumor tumor-promoting properties, emerging adaptive growth responses, sleep regulation, adult The annotation TNF as an adipokine indisputable contribution obesity- cancer-associated metabolic diseases have provoked new area research focusing on dual function regulating immunity energy Here, discuss TNFR signaling coupling immune processes might be relevant adaption host environmental stresses, or, case obesity, promote derangements disease.

Язык: Английский

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Damage control of epithelial barrier function in dynamic environments

European Journal of Cell Biology, Год журнала: 2024, Номер 103(2), С. 151410 - 151410

Опубликована: Апрель 3, 2024

Epithelial tissues cover the surfaces and lumens of internal organs multicellular animals crucially contribute to environment homeostasis by delineating distinct compartments within body. This vital role is known as epithelial barrier function. cells are arranged like cobblestones intricately bind together form an sheet that upholds this Central restriction solute fluid diffusion through intercellular spaces occluding junctions, tight junctions in vertebrates septate invertebrates. As part tissues, undergo constant renewal, with older being replaced new ones. Simultaneously, tissue undergoes relative rearrangement, elongating, shifting directionally a whole. The movement or shape changes necessitate significant deformation reconnection junctions. Recent advancements have shed light on intricate mechanisms which sustain their function dynamic environments. review aims introduce these noteworthy findings discuss some questions remain unanswered.

Язык: Английский

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Cell polarity and extrusion: How to polarize extrusion and extrude misspolarized cells?

Current topics in developmental biology/Current Topics in Developmental Biology, Год журнала: 2023, Номер unknown, С. 131 - 167

Опубликована: Янв. 1, 2023

Язык: Английский

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Epithelial cell-fate switch triggering ectopic ligand-receptor-mediated JAK-STAT signaling promotes tumorigenesis in Drosophila

iScience, Год журнала: 2025, Номер 28(4), С. 112191 - 112191

Опубликована: Март 11, 2025

Disruption of epithelial architecture is a hallmark human malignant cancers, yet whether and how deformation influences tumor progression has been elusive. Here, through genetic screen in Drosophila eye disc, we explored mutations that potently promoted Ras-activated (RasV12) growth identified eyes absent (eya), an determination gene, whose mutation compromised tissue but synergized with RasV12 to cause massive overgrowth. Furthermore, induction cell-fate switch by mis-expression Abd-B the disc also induced Mechanistically, caused invagination accompanied partial mislocalization transmembrane receptor Domeless (Dome) from apical basal membrane epithelium, where its ligand Unpaired3 (Upd3) present. This led JAK-STAT activation cooperates drive progression. Our data provide mechanistic explanation for subsequent creates cancer-prone environment epithelium.

Язык: Английский

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In vivomeasurements of receptor tyrosine kinase activity reveal feedback regulation of a developmental gradient

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

A lack of tools for detecting receptor activity in vivo has limited our ability to fully explore receptor-level control developmental patterning. Here, we extend a new class biosensors tyrosine kinase (RTK) activity, the pYtag system, visualize endogenous RTK Drosophila . We build three RTKs that function across stages and tissues. By characterizing Torso::pYtag during terminal patterning early embryo, find Torso differs from downstream ERK two surprising ways: is narrowly restricted poles but produces broader gradient ERK, decreases over time while sustained. This decrease driven by pathway-dependent negative feedback. Our results suggest an updated model where narrow domain tuned amplitude feedback, locally activates signaling effectors which diffuse through syncytial embryo form gradient. Altogether, this work highlights usefulness pYtags investigating regulation

Язык: Английский

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Epithelial cell competition is promoted by signaling from immune cells

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 18, 2025

Abstract In epithelial tissues, juxtaposition of cells different phenotypes can trigger cell competition, a process whereby one type drives death and extrusion another. During growth homeostasis, competition is thought to serve quality control function, eliminating that are “less fit”. Tissues may also attack eliminate newly arising tumor cells, exploiting mechanisms shared with other instances but differ, reportedly, in the involvement immune system. Whereas have been shown play direct role killing this has not observed cases suggesting tissues recognize handle cancer differently. Here, we challenge view, showing that, fruit fly Drosophila , innate similar roles during classical as tumors. These findings suggest suppression exploit same involved promoting phenotypic uniformity among cells.

Язык: Английский

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Oncogenic Ras, Yki and Notch signals converge to confer clone competitiveness through Upd2

Journal of genetics and genomics/Journal of Genetics and Genomics, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

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Ribosomal protein mutations and cell competition: autonomous and nonautonomous effects on a stress response

Genetics, Год журнала: 2023, Номер 224(3)

Опубликована: Июнь 2, 2023

Abstract Ribosomal proteins (Rps) are essential for viability. Genetic mutations affecting Rp genes were first discovered in Drosophila, where they represent a major class of haploinsufficient mutations. One mutant copy gives rise to the dominant “Minute” phenotype, characterized by slow growth and small, thin bristles. Wild-type (WT) Minute cells compete mosaics, that is, Rp+/− preferentially lost when their neighbors wild-type genotype. Many features gene haploinsufficiency (i.e. phenotypes) mediated transcriptional program. In reduced translation under control Xrp1, bZip-domain transcription factor induced leads ultimately phosphorylation eIF2α consequently inhibition most translation. phenotypes also transcriptionally yeast mammals. mammals, Impaired Ribosome Biogenesis Checkpoint activates p53. Recent findings link other cellular stresses, including DNA damage response endoplasmic reticulum stress. We suggest cell competition results from nonautonomous inputs stress responses, bringing decisions between adaptive apoptotic outcomes influence nearby cells. eliminates aneuploid which loss chromosome haploinsufficiency. The effects on whole organism, flies or humans with Diamond-Blackfan Anemia, may be inevitable consequences pathways useful eliminating individual mosaics. Alternatively, apparently deleterious organism might adaptive, preventing even more detrimental outcomes. example, p53 activation appears suppress oncogenic

Язык: Английский

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