Biology subjects

Guillou, A.

Publications and source records attributed to Guillou, A..

7 recordsLinked to original sources

bioRxiv2026

Delta/Notch signaling level is decoded through transcriptional burst duration during muscle progenitor specification

The ability of progenitor cells to interpret different levels of signaling pathway activity is fundamental to the generation of cellular diversity during development. Muscle progenitors, for example, are exposed to different levels of signals from their microenvironment. However, how they decode these quantitative differences to regulate their cellular behaviors during myogenesis remains poorly understood. Here, we addressed this question during the specification of two populations of Drosophila adult muscle progenitors (AMPs). We found that, despite being spatially adjacent, indirect flight muscle (IFM) and direct flight muscle (DFM) progenitors receive distinct levels of Notch signaling. We further show that the spatial distribution of epithelial Delta contributes to differential Notch activation. Higher Delta levels adjacent to IFM progenitors promote stronger Notch signaling. To investigate how these quantitative differences are translated into transcriptional responses, we developed a Notch-responsive MS2 reporter to monitor transcription in living AMPs. Our measurements reveal that Notch-dependent transcription occurs in stochastic bursts, with IFM progenitors displaying longer but less frequent bursts than DFM progenitors. Strikingly, equalizing epithelial Delta levels abolished differences between the two populations in both Notch-dependent transcriptional activity and the protein levels of Notch target genes. Together, our findings suggest that quantitative differences in signaling may be translated into distinct transcriptional outputs through modulation of transcriptional bursting. This may represent a mechanism by which a single signaling pathway can be deployed to regulate diverse cellular responses during development.

developmental biology↗

bioRxiv2026

The Endoplasmic Reticulum as a Cytoplasmic Anchor for Microtubule-Driven Aster Centration

The proper positioning of microtubule (MT) asters is essential to regulate division positioning and multi-cellular morphogenesis, yet the mechanisms regulating this process remain poorly understood. Using sea urchin zygotes as a model, we combined high-resolution imaging, perturbation assays, and 3D modeling to investigate the nature of forces driving sperm aster centration after fertilization. We show that centering asters are highly anisotropic, featuring long microtubules extending at the aster front that may engage with organelles in bulk cytoplasm to generate pulling forces. While vesicular compartments, like acidic organelles, mitochondria or yolk, contributed minimally, we found that the endoplasmic reticulum (ER) undergoes a massive compaction around the centering aster and drags cytosol to produce a reactive centering force on the aster. Perturbing ER organization by cytoplasmic stratification or Atlastin-mediated fragmentation disrupted aster centration. A two-fluid model suggests that the frictional interaction between the compacting ER and cytosol fluid is sufficient to recapitulate key features of aster centration. These findings identify the ER as an important cytoplasmic anchor for MT force exertion in bulk cytoplasm, to guide aster centering motion and influence early embryonic division geometries. More broadly, our results highlight the role of cytoplasmic architecture in shaping the mechanics of organelle positioning during development.

cell biology↗

bioRxiv2026

SPARC mediates tumour-stroma intercellular communication through endosomal regulation of Delta and Notch signalling

Tumour progression relies on reciprocal communication between genetically altered cancer cells and surrounding stromal cells. While the genetic alterations that initiate tumorigenesis have been extensively studied, the dysregulated feedback signalling provided by co-opted stromal cells remains poorly understood. Here, we used a Drosophila cancer model to address this question and identified the matricellular protein SPARC as a mediator of tumour-stroma communication. SPARC is produced by mesenchymal cells and transferred into epithelial tumour cells, where it is internalized through the endocytic pathway. Following uptake, SPARC accumulates in Rab7 positive late endosomes and colocalize with the Notch ligand Delta. SPARC internalization promotes endosomal enlargement and reduces endosome dynamics. Increased SPARC levels in epithelial tumours indirectly attenuate Notch signalling activity through at least altered Delta trafficking. We further identify the N-terminal acidic domain of SPARC as specifically required for its targeting to Delta-associated endosomes. Together, our findings uncover a stromal feedback mechanism by which SPARC modulates Notch signalling through endosomal regulation during tumour development.

developmental biology↗

bioRxiv2025

Immune tracheal intercellular signalling coordinates the muscle injury response in Drosophila

In skeletal muscle, immune and vascular responses are essential for regeneration, yet the cellular and molecular mechanisms that coordinate their activities to restore tissue function remain unclear. Here, using Drosophila, we uncover a multi-organ signaling program that integrates muscle fibers, macrophages, vascular-like tracheal cells, and the extracellular matrix (ECM) to maintain muscle function in response to acute damage. Muscle injury induces rapid macrophage recruitment and secretion of the FGF-like ligand Branchless (Bnl), which activates FGF/FGFR signalling in tracheal cells and promotes their targeted expansion toward damaged muscle. Concomitantly, macrophages deposit ECM components on the damaged muscle, including Collagen IV, forming a localized microenvironment that restricts Bnl ligand diffusion and facilitates directed tracheal remodelling. Genetic disruption of macrophage-derived Bnl or macrophage-mediated ECM deposition abolishes tracheal remodelling and compromises muscle function following injury. Together, these findings reveal a novel immune-vascular communication program in which macrophages coordinate fibroblast growth factor signalling and ECM organization to shape muscle microenvironment and preserve muscle function following acute damage.

developmental biology↗

bioRxiv2025

Monitoring Whole-Body Inflammation with Gallium-68 Labeled Polydopamine Iron Oxide Particles via Hybrid Immuno-PET-MRI

Monitoring immune reactions via inflammation imaging provides valuable disease prognosis but remains limited by currently available probes and imaging capabilities. In this study, a bimodal imaging probe was developed from microsized polydopamine matrix-based magnetic particles (M3P) functionalized with antibodies that target vascular cell adhesion molecule-1 (VCAM-1) and that are radiolabeled with the radioisotope Gallium-68. This probe combines sensitive inflammation detection via Positron Emission Tomography (immuno-PET) and high-resolution mapping via Magnetic Resonance Imaging (immuno-MRI). The probe represents a powerful disease diagnosis tool to assess the status of systemic inflammation in sepsis as whole-body immuno-PET enables rapid evaluation of the situation, and immuno-MRI provides a more detailed characterization of the identified affected tissues. The elimination profile of the M3P probe is restricted to the mononuclear phagocyte system and does not undergo renal clearance, which is suitable for application in kidney disorders. The efficacy of the hybrid immuno-PET-MRI diagnosis protocol was tested in a murine model of rhabdomyolysis. Kidney inflammation was detected by whole-body immuno-PET, and vascular inflammation patterns could be revealed by high-resolution immuno-MRI. This bimodal PET-MRI probe could significantly improve inflammation monitoring in pathologies characterized by systemic inflammation or lung and kidney dysfunction.

bioengineering↗

bioRxiv2019

Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

During pregnancy, maternal metabolic diseases and hormonal imbalance may alter fetal beta cell development and/or proliferation, thus leading to an increased risk for developing type 2 diabetes in adulthood. Although thyroid hormones play an important role in fetal endocrine pancreas development, the impact of maternal hypothyroidism on glucose homeostasis in adult offsprings remains poorly understood. Here, we show that when fed normal chow, adult mice born to hypothyroid mothers were more glucose-tolerant due to beta cell hyperproliferation and increased insulin sensitivity. However, following high fat feeding, these offsprings became profoundly hyperinsulinemic, insulin-resistant and glucose-intolerant compared to controls from euthyroid mothers. Suggesting presence of epigenetic changes, altered glucose metabolism was maintained in a second generation of animals. As such, gestational hypothyroidism induces long-term and persistent alterations in endocrine pancreas function, which may have important implications for type 2 diabetes prevention in affected individuals.\n\nSIGNIFICANCEDiabetes and hypothyroidism are two major public health issues, affecting [~] 9 and 2 % of the population worldwide, respectively. As master metabolic gatekeepers, the thyroid hormones play an essential role in metabolism and fetal development. However, gestation increases demand on the thyroid axis in the mother, leading to hypothyroidism in 0.5 % of pregnancies. Maternal hypothyroidism is associated with deficits in fetal growth that may lead to long-term alterations in metabolism in the offspring. We therefore sought to investigate the effects of gestational hypothyroidism on glucose metabolism in adult offspring and their descendants, and how this may predispose to diabetes development.

physiology↗

bioRxiv2018

3 minutes to precisely measure morphogen concentration

Morphogen gradients provide concentration-dependent positional information along polarity axes. Although the dynamics of establishment of these gradients is well described, precision and noise in the downstream activation processes remain elusive. A simple paradigm to address these questions is the Bicoid morphogen gradient that elicits a rapid step-like transcriptional response in young fruit fly embryos. Focusing on the expression of the main Bicoid target, hunchback (hb), at the onset of zygotic transcription, we used the MS2-MCP approach which combines fluorescent labeling of nascent mRNA with live imaging at high spatial and temporal resolution. Removing 36 putative Zelda binding sites unexpectedly present in the original MS2 reporter, we show that the 750 bp of the hb promoter are sufficient to recapitulate endogenous expression at the onset of zygotic transcription. After each mitosis, in the anterior, expression is turned on to rapidly reach a plateau with all nuclei expressing the reporter. Consistent with a Bicoid dose-dependent activation process, the time period required to reach the plateau increases with the distance to the anterior pole. Remarkably, despite the challenge imposed by frequent mitoses and high nuclei-to-nuclei variability in transcription kinetics, it only takes 3 minutes at each interphase for the MS2 reporter loci to measure subtle differences in Bicoid concentration and establish a steadily positioned and steep (Hill coefficient ~ 7) expression boundary. Modeling based on cooperativity between the 6 known Bicoid binding sites in the hb promoter region and assuming rate limiting concentrations of the Bicoid transcription factor at the boundary is able to capture the observed dynamics of pattern establishment but not the steepness of the boundary. This suggests that additional mechanisms are involved in the steepness of the response.

developmental biology↗