Biology subjects

Cumming, T.

Publications and source records attributed to Cumming, T..

3 recordsLinked to original sources

bioRxiv2026

EpiCure (Epithelial Curation): a versatile and handy tool for curation of epithelial segmentation

Investigating single-cell dynamics and morphology in tissues and embryos requires highly accurate quantitative analysis of microscopy images. Despite significant advances in the field of bioimage analysis, even the most sophisticated segmentation and tracking algorithms inevitably produce errors (e.g. : over segmentation, missing objects, miss-connected objects). Although error rate may be small, their propagation throughout a time-lapse sequence has catastrophic effects on the accuracy of tracking and extraction of single cell parameters. Extracting single cell temporal information in the context of tissue/embryo requires thus expert curation to identify and correct segmentation errors. In the movies commonly used in developmental biology and stem cell research, both the number of imaged cells and the duration of recording are large, making this manual correction task extremely time-consuming. This has now become a major bottleneck in the fields of development, stem cell biology and bioimage analysis. We present here EpiCure (Epithelial Curation), a versatile tool designed to streamline and accelerate manual curation of segmentation and tracking in 2D movies of large epithelial tissues. EpiCure uses temporal information and morphometric parameters to automatically identify segmentation and tracking errors and provides user-friendly tools to correct them. It focuses on ergonomics and offers several visualization options to help navigating in movies of tissue covering a large number of cells, speeding up the detection of errors and their curation. EpiCure is highly interoperable and supports input from a wide range of segmentation tools. It also includes multiple export filters, enabling seamless integration with downstream analysis pipelines. In this paper, using movies from several animal models, we highlight the importance of curating cell segmentation and tracking for accurate downstream analysis, and demonstrate how EpiCure helps the curation process for extracting accurate single cell dynamics and cellular events detection, making it faster and amenable on large dataset.

developmental biology↗

bioRxiv2025

Integration of past caspase activity biases cell elimination in vivo

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

developmental biology↗

bioRxiv2022

Patterned apoptosis modulates local growth and tissue shape in a fast-growing epithelium

What regulates organ size and shape remains one of the fundamental mysteries of modern biology. So far, research in this area has primarily focused on deciphering the regulation in time and space of growth and cell division, while the contribution of cell death has been much more neglected. This includes studies of the Drosophila wing imaginal disc, the prospective fly wing which undergoes massive growth during larval stage, and represents one of the best characterised systems for the study of growth and patterning. So far, it has been assumed that cell death was relatively neglectable in this tissue and as a result the pattern of growth was usually attributed to the distribution of cell division. Here, using systematic mapping and registration combined with quantitative assessment of clone size and disappearance, we show for the first time that cell death is not neglectable, and outline a persistent pattern of cell death and clone elimination in the disc. Local variation of cell death is associated with local variation of clone size, pointing to an impact of cell death on local growth which is not fully compensated by proliferation. Using morphometric analyses of adult wing shape and genetic perturbations, we provide evidence that patterned death affects locally and globally adult wing shape and size. This study describes a roadmap for accurate assessment of the contribution of cell death to tissue shape, and outlines for the first time an important instructive role of cell death in modulating quantitatively local growth and the morphogenesis of a fast-growing tissue.

developmental biology↗