Biology subjects

Perochon, J.

Publications and source records attributed to Perochon, J..

6 recordsLinked to original sources

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

Intestinal Tissue Mechanics Regulate Angiogenesis and Stem Cell Proliferation via Vascular Piezo

The vasculature is a prominent component of developmental and adult tissue microenvironments. How tissue specific characteristics and environmental states influence vascular biology and function, remains largely understudied. Using the fruit fly Drosophila melanogaster midgut and its associated vascular-like tracheal system, we discover reciprocal, mechanochemical interorgan communication between the adult intestine and its vascular microenvironment, which influences vascular and stem cell adaptations during intestinal regeneration. Mechanistically, apoptotic epithelial cells contribute to biomechanical remodelling of the regenerating midgut, which is associated with activation of Piezo in a subset of gut tracheal cells. Piezo drives activation of the mechanosensitive transcription factor Yorkie/YAP, leading to tracheal remodelling and intestinal stem cell proliferation. Furthermore, we identify a conserved role of mammalian vascular Piezo1 influencing remodelling of the intestinal crypt vasculature, and intestinal regeneration upon DNA damage and inflammation in mice. Our cross-species in vivo study reveals the presence of biomechanically distinct compartments in the regenerative intestine and identifies mechanosensory interorgan signalling, which contributes to intestinal regeneration through the vascular-stem cell niche. Furthermore, our work highlights the importance of studying tissue- and context-specific vascular biology to better understand intestinal compartmentalization, plasticity, and the complexity of tissue/vasculature interactions within a living organ.

developmental biology↗

bioRxiv2024

Neuroendocrine Control of Intestinal Regeneration Through the Vascular Niche in Drosophila.

Robust and controlled intestinal regeneration is essential for the preservation of organismal health and wellbeing and involves reciprocal interactions between the intestinal epithelium and its microenvironment. While knowledge of regulatory roles of the microenvironment on the intestine is vast, how distinct perturbations within the intestinal epithelium may influence tailored responses from the microenvironment, remains understudied. Here, we present previously unknown signaling between enteroendocrine cells (EE), vasculature-like trachea (TTCs), and neurons, which drives regional and global stem cell proliferation during adult intestinal regeneration in Drosophila. Injury-induced ROS from midgut epithelial cells promotes the production and secretion of Dh31, the homolog of mammalian Calcitonin Gene-Related Peptide (CGRP), from anterior midgut EE cells. Dh31 from EE cells and neurons signal to Dh31 receptor within TTCs leading to cell autonomous production of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)-like Pvf1. Tracheal derived Pvf1 induces remodeling of the tracheal stem cell niche and regenerative ISC proliferation through autocrine and paracrine Pvr/MAPK signalling, respectively. Interestingly, while EE Dh31 exerts broad control of ISC proliferation throughout the midgut, functions of the neuronal source of the ligand appear restricted to the posterior midgut. Altogether, our work has led to the discovery of a novel enteroendocrine/neuronal/vascular signaling network controlling global and domain specific ISC proliferation during adult intestinal regeneration.

developmental biology↗

bioRxiv2023

Phosphogluconolactonase as the linchpin of an efficient pentose phosphate pathway

The metabolic networks of microorganisms are remarkably robust to genetic and environmental perturbations. This robustness stems from redundancies such as gene duplications, isoenzymes, alternative metabolic pathways, and also from non-enzymatic reactions. In the oxidative branch of the pentose-phosphate pathway (oxPPP), 6-phosphogluconolactone hydrolysis into 6-phosphogluconate is catalysed by 6-phosphogluconolactonase (Pgl) but in the absence of the latter, the oxPPP flux is thought to be maintained by spontaneous hydrolysis. However, in {Delta}pgl Escherichia coli, an extracellular pathway can also contribute to pentose-phosphate synthesis. This raises question as to whether the intracellular non-enzymatic reaction can compensate for the absence of 6-phosphogluconolactonase and, ultimately, on the role of 6-phosphogluconolactonase in central metabolism. Our results validate that the bypass pathway is active in the absence of Pgl, specifically involving the extracellular spontaneous hydrolysis of gluconolactones to gluconate. Under these conditions, metabolic flux analysis reveals that this bypass pathway accounts for the entire flux into the oxPPP. This alternative metabolic route - partially extracellular - sustains the flux through the oxPPP necessary for cell growth, albeit at a reduced rate in the absence of Pgl. Importantly, these findings imply that intracellular non-enzymatic hydrolysis of 6-phosphogluconolactone does not compensate for the absence of Pgl. This underscores the crucial role of Pgl in ensuring the efficient functioning of the oxPPP.

biochemistry↗

bioRxiv2021

Functional analysis of deoxyhexose sugar utilization in Escherichia coli reveals fermentative metabolism under aerobic conditions

L-rhamnose and L-fucose are the two main 6-deoxyhexoses Escherichia coli can use as carbon and energy sources. Deoxyhexose metabolism leads to the formation of lactaldehyde whose fate depends on oxygen availability. Under anaerobic conditions, lactaldehyde is reduced to 1,2-propanediol whereas under aerobic condition, it should be oxidised into lactate and then channelled into the central metabolism. However, although this all-or-nothing view is accepted in the literature, it seems overly simplistic since propanediol is also reported to be present in the culture medium during aerobic growth on L-fucose. To clarify the functioning of 6-deoxyhexose sugar metabolism, a quantitative metabolic analysis was performed to determine extra- and intracellular fluxes in E. coli K-12 MG1655 (a laboratory strain) and in E. coli Nissle 1917 (a human commensal strain) during anaerobic and aerobic growth on L-rhamnose and L-fucose. As expected, lactaldehyde is fully reduced to 1,2-propanediol in anoxic conditions allowing complete reoxidation of the NADH produced by glyceraldehyde-3-phosphate-dehydrogenase. We also found that net ATP synthesis is ensured by acetate production. More surprisingly, lactaldehyde is also primarily reduced into 1,2-propanediol under aerobic conditions. For growth on L-fucose, 13C-metabolic flux analysis revealed a large excess of available energy, highlighting the need to better characterize ATP utilization processes. The probiotic E. coli Nissle 1917 strain exhibits similar metabolic traits, indicating that they are not the result of the K-12 strains prolonged laboratory use. IMPORTANCEE. colis ability to survive, grow and colonize the gastrointestinal tract stems from its use of partially digested food and hydrolysed glycosylated proteins (mucins) from the intestinal mucus layer as substrates. These include L-fucose and L-rhamnose, two 6-deoxyhexose sugars, whose catabolic pathways have been established by genetic and biochemical studies. However, the functioning of these pathways has only partially been elucidated. Our quantitative metabolic analysis provides a comprehensive picture of 6-deoxyhexose sugar metabolism in E. coli under anaerobic and aerobic conditions. We found that 1,2-propanediol is a major by-product under both conditions, revealing the key role of fermentative pathways in 6-deoxyhexose sugar metabolism. This metabolic trait is shared by both E. coli strains studied here, a laboratory strain and a probiotic strain. Our findings add to our understanding of E. colis metabolism and of its functioning in the bacteriums natural environment.

physiology↗

bioRxiv2021

Dynamic adult tracheal plasticity drives stem cell adaptation to changes in intestinal homeostasis.

Coordination of stem cell function by local and niche-derived signals is essential to preserve adult tissue homeostasis and organismal health. The vasculature is a prominent component of multiple stem cell niches. However, its role in adult intestinal homeostasis remains largely understudied. Here, we uncover a previously unrecognised crosstalk between adult intestinal stem cells (ISCs) in Drosophila and the vasculature-like tracheal system, which is essential for intestinal regeneration. Following damage to the intestinal epithelium, gut-derived reactive oxygen species (ROS) activate tracheal HIF-1 and bidirectional FGF/FGFR signaling, leading to reversible remodelling of gut-associated terminal tracheal cells and ISC proliferation following damage. Unexpectedly, ROS-induced adult tracheal plasticity involves downregulation of the tracheal specification factor trachealess (trh) and upregulation of IGF2 mRNA-binding protein (IGF2BP2/Imp). Our results reveal a novel intestine/vasculature interorgan communication program, which is essential to adapt stem cells response to the proliferative demands of the intestinal epithelium.

developmental biology↗