Biology subjects

Cadart, C.

Publications and source records attributed to Cadart, C..

6 recordsLinked to original sources

bioRxiv2025

A novel mechanism for centrosome expulsion ensures metabolic activity in polyploid cells

Programmed polyploidy is often linked to increase cell size to support enhanced metabolism, barrier function or regeneration. In certain polyploid cells, the cytoskeleton is drastically remodeled-most notably by eliminating centrosomes. However, the purpose and mechanisms underlying centrosome elimination have remained unclear. We investigated this question in Drosophila acentrosomal salivary glands (SGs), a physiological polyploid model where cells reach high chromosome content through endoreplication. Using genetic tools, live imaging approaches, super-resolution microscopy combined with tissue clearing and electron microscopy, our study uncovers a novel centrosome elimination pathway in vivo. This process requires non-muscle myosin II (MyoII) activity and the macroautophagic machinery to drive centrosome release into the lumen of the salivary glands via autolysosomal exocytosis. Failure to eliminate centrosomes disrupts the mitochondria network, impairing respiration and ATP production. Our findings reveal a previously unknown mechanism that removes centrosomes through the secretory autophagy pathway to protect mitochondrial function and support the high metabolic demands of polyploid cells.

cell biology↗

bioRxiv2022

Ploidy modulates cell size and metabolic rate in Xenopus embryos

A positive correlation between genome size and cell size is well documented, but impacts on animal physiology are poorly understood. In Xenopus frogs, the number of genome copies (ploidy) varies across species and can be manipulated within a species. Here we show that triploid tadpoles contain fewer, larger cells than diploids and consume oxygen at a lower rate. Treatments that altered cell membrane stability or electrical potential abolished this difference, suggesting that a decrease in total cell surface area reduces basal energy consumption in triploids. Comparison of Xenopus species that evolved through polyploidization revealed that metabolic differences emerged during development when cell size scaled with genome size. Thus, ploidy affects metabolism by altering the cell surface area to volume ratio in a multicellular organism. One-Sentence SummaryThe amount of DNA per cell in a vertebrate modulates basal metabolism by altering cell size and plasma membrane energetics.

cell biology↗

bioRxiv2022

Dodecaploid Xenopus longipes provides insight into the emergence of size scaling relationships during development

Genome and cell size are strongly correlated across species1-6 and influence physiological traits like developmental rate7-12. Although size scaling features such as the nuclear-cytoplasmic (N/C) ratio are precisely maintained in adult tissues13, it is unclear when during embryonic development size scaling relationships are established. Frogs of the genus Xenopus provide a model to investigate this question, since 29 extant Xenopus species vary in ploidy from 2 to 12 copies (n) of the genome, ranging from 20 to 108 chromosomes14,15. The most widely studied species, X. laevis (4n=36) and X. tropicalis (2n=20), scale at all levels from body size to cellular and subcellular16. Paradoxically, the rare, critically endangered dodecaploid (2n=108) X. longipes is a small frog15,17. We observed that despite some morphological differences, X. longipes and X. laevis embryogenesis occurred with similar timing, with genome to cell size scaling emerging at the swimming tadpole stage. Across the three species, cell size was determined primarily by egg size, while nuclear size correlated with genome size during embryogenesis, resulting in different nuclear-cytoplasmic ratios at the mid-blastula transition. At the subcellular level, nuclear size correlated more strongly with genome size, whereas mitotic spindle size scaled with cell size. Our cross-species study indicates that scaling of cell size to ploidy is not due to abrupt changes in cell division timing, that different size scaling regimes occur during embryogenesis, and that the developmental program of Xenopus is remarkably consistent across a wide range of genome and egg sizes. ONE SENTENCE SUMMARYComparison of size metrics in embryos from different ploidy Xenopus species, including the dodecaploid X. longipes, reveals distinct size scaling regimes during development.

developmental biology↗

bioRxiv2021

Volume growth in animal cells is cell cycle dependent and shows additive fluctuations

The way proliferating animal cells coordinate the growth of their mass, volume, and other relevant size parameters is a long-standing question in biology. Studies focusing on cell mass have identified patterns of mass growth as a function of time and cell cycle phase, but little is known about volume growth. To address this question, we improved our fluorescence exclusion method of volume measurement (FXm) and obtained 1700 single-cell volume growth trajectories of HeLa cells. We find that, during most of the cell cycle, volume growth is close to exponential and proceeds at a higher rate in S-G2 than in G1. Comparing the data with a mathematical model, we establish that the cell-to-cell variability in volume growth arises from constant-amplitude fluctuations in volume steps, rather than fluctuations of the underlying specific growth rate. We hypothesize that such "additive noise" could emerge from the processes that regulate volume adaptation to biophysical cues, such as tension or osmotic pressure.

cell biology↗

bioRxiv2020

Compromised nuclear envelope integrity drives tumor cell invasion

While mutations leading to a fragile envelope of the cell nucleus are well known to cause diseases such as muscular dystrophies or accelerated aging, the pathophysiological consequences of the recently discovered mechanically induced nuclear envelope ruptures in cells harboring no mutation are less known. Here we show that repeated loss of nuclear envelope integrity in nuclei experiencing mechanical constraints promotes senescence in nontransformed cells, and induces an invasive phenotype including increased collagen degradation in human breast cancer cells, both in vitro and in a mouse xenograft model of breast cancer progression. We show that these phenotypic changes are due to the presence of chronic DNA damage and activation of the ATM kinase. In addition, we found that depletion of the cytoplasmic exonuclease TREX1 is sufficient to abolish the DNA damage in mechanically challenged nuclei and to suppress the phenotypes associated with the loss of nuclear envelope integrity. Our results also show that TREX1-dependent DNA damage induced by physical confinement of tumor cells inside the mammary duct drives the progression of in situ breast carcinoma to the invasive stage. We propose that DNA damage in mechanically challenged nuclei could affect the pathophysiology of crowded tissues by modulating proliferation and extracellular matrix degradation of normal and transformed cells.

cell biology↗

bioRxiv2017

An adder behavior in mammalian cells achieves size control by modulation of growth rate and cell cycle duration

Despite decades of research, it remains unclear how mammalian cell growth varies with cell size and across the cell division cycle to maintain size control. Answers have been limited by the difficulty of directly measuring growth at the single cell level. Here we report direct measurement of single cell volumes over complete cell division cycles. The volume added across the cell cycle was independent of cell birth size, a size homeostasis behavior called \"adder\". Single-cell growth curves revealed that the homeostatic behavior relied on adaptation of G1 duration as well as growth rate modulations. We developed a general mathematical framework that characterizes size homeostasis behaviors. Applying it on datasets ranging from bacteria to mammalian cells revealed that a near-adder is the most common type of size control, but only mammalian cells achieve it using modulation of both cell growth rate and cell-cycle progression.

cell biology↗