Biology subjects

Gilquin, L.

Publications and source records attributed to Gilquin, L..

5 recordsLinked to original sources

bioRxiv2026

OrganScaleR: An Open Shiny Tool for Principled Organ-Weight Inference in Mouse Physiology

BackgroundOrgan weights are often divided by body weight to report "relative" organ size. Yet ratios usually stay size-dependent and become misleading. We built a simple decision path for size adjustment and wrapped it in a Shiny application so physiologists can get correct answers without coding. MethodsWe reused liver and body-weight data from a mouse nutrition study for confirmatory examples in two common cases: when diet groups shared a wide body-size range, and when diet produced much smaller animals with little overlap. We compared liver-to-body-weight ratios with size-adjusted regression when the body-size overlap allowed comparisons, and with causal Bayesian mediation when it did not. The full workflow was implemented in OrganScaleR, a guided R Shiny application. ResultsThe ratio-normalized organ weight is still associated with body weight, leading to misleading comparisons. Modeling liver weight against body weight gave more cautious, size-adjusted effects when groups shared a common size range. When diets shifted body size strongly and overlap was limited, causal mediation showed that most organ differences followed the change in body weight rather than an organ-specific action. Simulations confirmed that ratios can generate false positives and biased estimates under allometric scaling, while model-based approaches remained reliable. OrganScaleR implements this decision workflow in a guided Shiny application that returns interpretable effects. ConclusionsOrganScaleR selects scale, enforces common support, and routes the analysis to size-adjusted ANCOVA or causal Bayesian mediation depending on body-weight overlap. It reports adjusted effects in original units through a point-and-click workflow, removing the statistical barrier to abandoning ratio normalization. HighlightsO_LIBody-weight ratios remain size-dependent and distort organ-weight comparisons. C_LIO_LIANCOVA at a common reference body weight removes ratio bias when groups overlap. C_LIO_LICausal mediation separates organ-specific from body-weight-mediated diet effects. C_LIO_LISimulations confirm ratios inflate false-positive rates under allometric scaling. C_LIO_LIOrganScaleR guides size adjustment without coding via a point-and-click workflow. C_LI

physiology↗

bioRxiv2026

Rewiring Fibroblast-Muscle Axis Drives Progressive Pathology in Bethlem Myopathy

Collagen VI-related myopathies, including Bethlem myopathy (BM), are progressive muscle disorders, but the mechanisms driving age-dependent disease progression remain poorly understood. Here, we used a zebrafish BM model carrying an exon-skipping mutation that generates a shorter collagen VI 1 chain and disrupts supramolecular assembly, recapitulating key features of the human disease. We further demonstrated that this model reproduces disease progression, with worsening muscle wasting, increased myofiber size variability, and age-associated skeletal deformities consistent with secondary consequences of muscle dysfunction rather than intrinsic bone defects. Single-nucleus RNA sequencing of trunk skeletal muscle revealed an early shift in cellular composition, with reduced myonuclei and increased fibroblast abundance, indicative of disease-associated aging. Myonuclei activated stress and quality control pathways, including autophagy and mitophagy, along with metabolic rewiring. In contrast, fibroblasts displayed early translational activation followed by progressive proteostatic and endoplasmic reticulum stress. At later stages, fibroblasts adopted a pro-fibrotic state, driving extracellular matrix remodeling and enhanced muscle-fibroblast communication. Consistently, analyses at the protein level confirmed early intracellular retention of the mutant protein, along with increased extracellular matrix deposition and fibrotic tissue formation in BM muscle. Among the three tested drugs targeting ER-stress and protein degradation, only TUDCA significantly ameliorated collagen VI deposition in the extracellular space in larvae. These findings identify fibroblasts as key drivers of disease progression and potential therapeutic targets.

developmental biology↗

bioRxiv2025

Characterizing drug activity with sensitive interactomes in human living cells

A number of human diseases results from abnormal protein-protein interactions (PPIs) involving key regulatory proteins. Therefore, an important strategy in therapeutics consists in developing inhibitory molecules that should ideally be specific for the aberrant PPI. In this context, it is critical to evaluate the number of PPIs that could be affected by the candidate molecule and to analyze the inhibitory potential before and after the formation of the PPI. Surprisingly, these two molecular aspects are rarely considered, due to a lack of appropriate methodological approaches. In this study, we present a novel methodology that captures drug-sensitive PPIs by considering drug-induced cellular functions in live cell conditions. As a proof-of-concept, we identified interactions of the human core signaling protein ERK1 that are specifically affected by two different inhibitory molecules. In addition, we used a complementary set of innovative tools that allowed visualizing the inhibitory effect on ERK1/cofactor protein complexes after their assembly in living cells. Overall, our work establishes a unique methodological approach for deciphering drug activity for potentially any target bait protein of interest.

molecular biology↗

bioRxiv2024

A nanobody-based approach to capture and visualize interactions of binary protein complexes in living cells

Protein interaction networks (or interactomes) are formed progressively, each interaction influencing the next one. Accordingly, a same protein will establish different interactomes depending on its first associated cofactor, thereby diversifying its function in the cell. In contrast to their central role, few methods exist to capture interactomes of dimeric protein complexes. Here, we tackle this issue by introducing an innovative method based on bimolecular fluorescence complementation and the specific binding of a nanobody fused to a proximity-dependent biotinylating enzyme. This method was applied to visualize and capture specific interactions of the cytoplasmic TAZ/14-3-3e and nuclear TAZ/TEAD2 complexes, which are major downstream effectors of the Hippo signaling pathway. Among other interactions, we identified SERPINB4 as a novel regulator of TAZ and 14-3-3e proliferative activity in mesenchymal stromal cells. Molecular dissections in living cells revealed the central role of a unique residue of TAZ for recruiting SERPINB4 specifically in the presence of 14-3-3e. Overall, our work demonstrates the importance of considering binary protein complexes for deciphering interactomes and establishes a novel sensitive method in this perspective.

molecular biology↗

bioRxiv2023

Dual-topology of collagen XV and tenascin C acts in concert to guide and shape developing motor axons

During development, motor axons are guided towards their muscle target by various extrinsic cues including extracellular matrix (ECM) proteins those identities remain poorly documented. Using single-cell RNA-sequencing of differentiating slow muscle progenitors (SMP) in zebrafish, we charaterized the SMP as a major source of ECM proteins that were computationally predicted to form a basement membrane-like structure tailored for motor axon guidance. Multiple in vivo and in vitro approaches further revealed that motor axon shape and growth relies on the timely expression of the attractive cue Collagen XV-B (ColXV-B) that locally provides motor axons with a permissive soft microenvironment and separately organizes the repulsive cue Tenascin C into a unique functional dual topology. Bioprinted micropatterns mimicking their unique topology provide compelling evidence that it represents a sufficient condition to elicit directional motor axon growth. Our study provides the first evidence that ECM topology and stiffness critically influence motor axon navigation in vertebrates with potential applications in regenerative medicine for peripheral nerve injury.

developmental biology↗