Search

Your search keyword '"Mayeuf-Louchart A"' showing total 120 results
Start Over Author "Mayeuf-Louchart A"
120 results on '"Mayeuf-Louchart A"'

3. MuscleJ2: a rebuilding of MuscleJ with new features for high-content analysis of skeletal muscle immunofluorescence slides

Author

Anne Danckaert, Aurélie Trignol, Guillaume Le Loher, Sébastien Loubens, Bart Staels, Hélène Duez, Spencer L. Shorte, and Alicia Mayeuf-Louchart

Subjects
Histology, Muscle fiber morphology, Centro- and perinuclei, Fiber typing, Vascularization, Phenotype cartography, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Histological analysis of skeletal muscle is of major interest for understanding its behavior in different pathophysiological conditions, such as the response to different environments or myopathies. In this context, many software programs have been developed to perform automated high-content analysis. We created MuscleJ, a macro that runs in ImageJ/Fiji on batches of images. MuscleJ is a multianalysis tool that initially allows the analysis of muscle fibers, capillaries, and satellite cells. Since its creation, it has been used in many studies, and we have further developed the software and added new features, which are presented in this article. We converted the macro into a Java-language plugin with an improved user interface. MuscleJ2 provides quantitative analysis of fibrosis, vascularization, and cell phenotype in whole muscle sections. It also performs analysis of the peri-myonuclei, the individual capillaries, and any staining in the muscle fibers, providing accurate quantification within regional sublocalizations of the fiber. A multicartography option allows users to visualize multiple results simultaneously. The plugin is freely available to the muscle science community.

Published
2023
Full Text
View/download PDF

5. NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression

Author

Alexis Boulinguiez, Christian Duhem, Alicia Mayeuf-Louchart, Benoit Pourcet, Yasmine Sebti, Kateryna Kondratska, Valérie Montel, Stéphane Delhaye, Quentin Thorel, Justine Beauchamp, Aurore Hebras, Marion Gimenez, Marie Couvelaere, Mathilde Zecchin, Lise Ferri, Natalia Prevarskaya, Anne Forand, Christel Gentil, Jessica Ohana, France Piétri-Rouxel, Bruno Bastide, Bart Staels, Helene Duez, and Steve Lancel

Subjects
Cell biology, Muscle biology, Medicine
Abstract

The sarcoplasmic reticulum (SR) plays an important role in calcium homeostasis. SR calcium mishandling is described in pathological conditions, such as myopathies. Here, we investigated whether the nuclear receptor subfamily 1 group D member (NR1D1, also called REV-ERBα) regulates skeletal muscle SR calcium homeostasis. Our data demonstrate that NR1D1 deficiency in mice impaired sarco/endoplasmic reticulum calcium ATPase–dependent (SERCA-dependent) SR calcium uptake. NR1D1 acts on calcium homeostasis by repressing the SERCA inhibitor myoregulin through direct binding to its promoter. Restoration of myoregulin counteracted the effects of NR1D1 overexpression on SR calcium content. Interestingly, myoblasts from patients with Duchenne muscular dystrophy displayed lower NR1D1 expression, whereas pharmacological NR1D1 activation ameliorated SR calcium homeostasis and improved muscle structure and function in dystrophic mdx/Utr+/– mice. Our findings demonstrate that NR1D1 regulates muscle SR calcium homeostasis, pointing to its therapeutic potential for mitigating myopathy.

Published
2022
Full Text
View/download PDF

8. Nuclear Receptor Subfamily 1 Group D Member 1 Regulates Circadian Activity of NLRP3 Inflammasome to Reduce the Severity of Fulminant Hepatitis in Mice

Author

Pourcet, Benoit, Zecchin, Mathilde, Ferri, Lise, Beauchamp, Justine, Sitaula, Sadicha, Billon, Cyrielle, Delhaye, Stéphane, Vanhoutte, Jonathan, Mayeuf-Louchart, Alicia, Thorel, Quentin, Haas, Joel T., Eeckhoute, Jérome, Dombrowicz, David, Duhem, Christian, Boulinguiez, Alexis, Lancel, Steve, Sebti, Yasmine, Burris, Thomas P., Staels, Bart, and Duez, Hélène M.

Published
2018
Full Text
View/download PDF

9. Influenza infection rewires energy metabolism and induces browning features in adipose cells and tissues

Author

Ayari, Asma, Rosa-Calatrava, Manuel, Lancel, Steve, Barthelemy, Johanna, Pizzorno, Andrés, Mayeuf-Louchart, Alicia, Baron, Morgane, Hot, David, Deruyter, Lucie, Soulard, Daphnée, Julien, Thomas, Faveeuw, Christelle, Molendi-Coste, Olivier, Dombrowicz, David, Sedano, Laura, Sencio, Valentin, Le Goffic, Ronan, Trottein, François, and Wolowczuk, Isabelle

Published
2020
Full Text
View/download PDF

10. MuscleJ: a high-content analysis method to study skeletal muscle with a new Fiji tool

Author

Alicia Mayeuf-Louchart, David Hardy, Quentin Thorel, Pascal Roux, Lorna Gueniot, David Briand, Aurélien Mazeraud, Adrien Bouglé, Spencer L. Shorte, Bart Staels, Fabrice Chrétien, Hélène Duez, and Anne Danckaert

Subjects
Skeletal muscle fiber, Histology, Image automated quantification, In situ cartography, Fiber typing, Satellite cells, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background Skeletal muscle has the capacity to adapt to environmental changes and regenerate upon injury. To study these processes, most experimental methods use quantification of parameters obtained from images of immunostained skeletal muscle. Muscle cross-sectional area, fiber typing, localization of nuclei within the muscle fiber, the number of vessels, and fiber-associated stem cells are used to assess muscle physiology. Manual quantification of these parameters is time consuming and only poorly reproducible. While current state-of-the-art software tools are unable to analyze all these parameters simultaneously, we have developed MuscleJ, a new bioinformatics tool to do so. Methods Running on the popular open source Fiji software platform, MuscleJ simultaneously analyzes parameters from immunofluorescent staining, imaged by different acquisition systems in a completely automated manner. Results After segmentation of muscle fibers, up to three other channels can be analyzed simultaneously. Dialog boxes make MuscleJ easy-to-use for biologists. In addition, we have implemented color in situ cartographies of results, allowing the user to directly visualize results on reconstituted muscle sections. Conclusion We report here that MuscleJ results were comparable to manual observations made by five experts. MuscleJ markedly enhances statistical analysis by allowing reliable comparison of skeletal muscle physiology-pathology results obtained from different laboratories using different acquisition systems. Providing fast robust multi-parameter analyses of skeletal muscle physiology-pathology, MuscleJ is available as a free tool for the skeletal muscle community.

Published
2018
Full Text
View/download PDF

11. The role of the nuclear receptor Rev-erbΑ during intraplaque neovascularization

Author

Bellengier, C., primary, Ferri, L., additional, Tardivel, M., additional, Bongiovanni, A., additional, Delhaye, S., additional, Duhem, C., additional, Thorel, Q., additional, Hebras, A., additional, Ram, B., additional, Amaouche, M., additional, Leriche, M., additional, Mayeuf-Louchart, A., additional, Sebti, Y., additional, Staels, B., additional, Duez, H., additional, and Pourcet, B., additional

Published
2023
Full Text
View/download PDF

12. Role of the nuclear receptor REV-ERB-Α in vascular calcification

Author

Ferri, L., primary, Bellengier, C., additional, Julla, J.-B., additional, Bongiovanni, A., additional, Delhaye, S., additional, Duhem, C., additional, Thorel, Q., additional, Hebras, A., additional, Leriche, M., additional, Ram, B., additional, Bicharel, M., additional, Amaouche, M., additional, Mayeuf-Louchart, A., additional, Sebti, Y., additional, Tardivel, M., additional, Venteclef, N., additional, Staels, B., additional, Gautier, J.-F., additional, Pourcet, B., additional, and Duez, H., additional

Published
2023
Full Text
View/download PDF

13. Glycogen Dynamics Drives Lipid Droplet Biogenesis during Brown Adipocyte Differentiation

Author

Alicia Mayeuf-Louchart, Steve Lancel, Yasmine Sebti, Benoit Pourcet, Anne Loyens, Stéphane Delhaye, Christian Duhem, Justine Beauchamp, Lise Ferri, Quentin Thorel, Alexis Boulinguiez, Mathilde Zecchin, Julie Dubois-Chevalier, Jérôme Eeckhoute, Logan T. Vaughn, Peter J. Roach, Christian Dani, Bartholomew A. Pederson, Stéphane D. Vincent, Bart Staels, and Hélène Duez

Subjects
Biology (General), QH301-705.5
Abstract

Summary: Browning induction or transplantation of brown adipose tissue (BAT) or brown/beige adipocytes derived from progenitor or induced pluripotent stem cells (iPSCs) can represent a powerful strategy to treat metabolic diseases. However, our poor understanding of the mechanisms that govern the differentiation and activation of brown adipocytes limits the development of such therapy. Various genetic factors controlling the differentiation of brown adipocytes have been identified, although most studies have been performed using in vitro cultured pre-adipocytes. We investigate here the differentiation of brown adipocytes from adipose progenitors in the mouse embryo. We demonstrate that the formation of multiple lipid droplets (LDs) is initiated within clusters of glycogen, which is degraded through glycophagy to provide the metabolic substrates essential for de novo lipogenesis and LD formation. Therefore, this study uncovers the role of glycogen in the generation of LDs. : Lipid droplet formation is a major feature of brown adipocyte differentiation. Mayeuf-Louchart et al. characterize the different steps of brown adipocyte differentiation in the mouse embryo and report the essential role of glycogen production and degradation by glycophagy for lipid droplet biogenesis. Keywords: brown adipose tissue, adipocyte differentiation, lipid droplet biogenesis, lipid, glycogen, autophagy, glycophagy, embryonic development, adipocyte metabolism, BAT

Published
2019
Full Text
View/download PDF

15. Role of bile acid receptor FXR in development and function of brown adipose tissue

Author

J, Yang, H D, de Vries, A, Mayeuf-Louchart, J H, Stroeve, V W, Bloks, M, Koehorst, H, Duez, B, Staels, F, Kuipers, T, van Zutphen, Health & Food, and Center for Liver, Digestive and Metabolic Diseases (CLDM)

Subjects
Bile Acids and Salts, Mice, Adipose Tissue, Brown, Infant, Newborn, Humans, Animals, Cell Biology, Molecular Biology, Receptors, G-Protein-Coupled, Signal Transduction
Abstract

Bile acids act as signalling molecules that contribute to maintenance of energy homeostasis in mice and humans. Activation of G-protein-coupled bile acid receptor TGR5 induces energy expenditure in brown adipose tissue (BAT). However, a role for the nuclear bile acid receptor Farnesoid X receptor (FXR) in BAT has remained ambiguous. We aimed to study the potential role of FXR in BAT development and functioning. Here we demonstrate low yet detectable expression of the α1/2 isoforms of FXR in murine BAT that markedly decreases upon cold exposure. Moderate adipose tissue-specific FXR overexpression in mice induces pronounced BAT whitening, presenting with large intracellular lipid droplets and extracellular collagen deposition. Expression of thermogenic marker genes including the target of Tgr5, Dio2, was significantly lower in BAT of chow-fed aP2-hFXR mice compared to wild-type controls. Transcriptomic analysis revealed marked up-regulation of extracellular matrix formation and down-regulation of mitochondrial functions in BAT from aP2-hFXR mice. In addition, markers of cell type lineages deriving from the dermomyotome, such as myocytes, as well as markers of cellular senescence were strongly induced. The response to cold and β3-adrenergic receptor agonism was blunted in these mice, yet resolved BAT whitening. Newborn cholestatic Cyp2c70-/- mice with a human-like bile acid profile also showed distinct BAT whitening and upregulation of myocyte-specific genes, while thermogenic markers were down-regulated. Ucp1 expression inversely correlated with plasma bile acid levels. Therefore, bile acid signalling via FXR has a role in BAT function already early in tissue development. Functionally, FXR activation appears to oppose TGR5-mediated thermogenesis.

Published
2023

16. NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression

Author

Boulinguiez, Alexis, primary, Duhem, Christian, additional, Mayeuf-Louchart, Alicia, additional, Pourcet, Benoit, additional, Sebti, Yasmine, additional, Kondratska, Kateryna, additional, Montel, Valérie, additional, Delhaye, Stéphane, additional, Thorel, Quentin, additional, Beauchamp, Justine, additional, Hebras, Aurore, additional, Gimenez, Marion, additional, Couvelaere, Marie, additional, Zecchin, Mathilde, additional, Ferri, Lise, additional, Prevarskaya, Natalia, additional, Forand, Anne, additional, Gentil, Christel, additional, Ohana, Jessica, additional, Piétri-Rouxel, France, additional, Bastide, Bruno, additional, Staels, Bart, additional, Duez, Helene, additional, and Lancel, Steve, additional

Published
2022
Full Text
View/download PDF

19. Reconstructing human Brown Fat developmental trajectory in vitro

Author

Jyoti Rao, Jerome Chal, Fabio Marchianò, Chih-Hao Wang, Ziad Al Tanoury, Svetlana Gapon, Yannis Djeffal, Alicia Mayeuf-Louchart, Ian Glass, Elizabeth M. Sefton, Bianca Habermann, Gabrielle Kardon, Fiona M. Watt, Yu-Hua Tseng, and Olivier Pourquié

Abstract

Brown adipocytes represent a specialized type of mammalian adipocytes able to uncouple nutrient catabolism from ATP generation to dissipate energy as heat. They play an important role in mammals, allowing non-shivering thermogenesis to regulate body temperature in response to cold exposure. In humans, the brown fat tissue is composed of small discrete depots found mostly throughout the neck and trunk region. Increasing brown fat activity either with drug treatment or cell therapy is considered a potential approach for the treatment of metabolic syndrome and obesity. The recent development of in vitro differentiation strategies relying on human pluripotent stem cells (hPSCs) offers the possibility to produce unlimited amounts of brown adipocytes. A strategy efficiently applied to several tissues is to recapitulate step by step the development of the tissue of interest by exposing hPSCs to the signaling cues used during normal embryonic development. However, this strategy has proven difficult to implement for brown fat as the development of this tissue is poorly understood. Here, we first used single cell RNA sequencing to characterize the development of interscapular brown fat in mouse. Our analysis identified a previously unrecognized population of brown adipocytes precursors characterized by expression of the transcription factor GATA6. We show that this precursor population can be efficiently generated from paraxial mesoderm precursors differentiated in vitro from hPSCs by modulating the signaling pathways identified in our transcriptomic analysis. These precursors can in turn be efficiently converted into functional brown adipocytes which can respond to adrenergic stimuli by increasing their metabolism resulting in heat production.

Published
2022

20. Reconstructing human Brown Fat developmental trajectory in vitro

Author

Rao, Jyoti, primary, Chal, Jerome, additional, Marchianò, Fabio, additional, Wang, Chih-Hao, additional, Al Tanoury, Ziad, additional, Gapon, Svetlana, additional, Djeffal, Yannis, additional, Mayeuf-Louchart, Alicia, additional, Glass, Ian, additional, Sefton, Elizabeth M., additional, Habermann, Bianca, additional, Kardon, Gabrielle, additional, Watt, Fiona M., additional, Tseng, Yu-Hua, additional, and Pourquié, Olivier, additional

Published
2022
Full Text
View/download PDF

22. Rev-erb-α controls skeletal muscle calcium homeostasis through myoregulin repression: implications in Duchenne Muscular Dystrophy

Author

Benoit Pourcet, Mathilde Zecchin, Kondratska K, Stéphane Delhaye, Piétri-Rouxel F, Montel, Alicia Mayeuf-Louchart, Bastide B, Lise Ferri, Alexis Boulinguiez, Quentin Thorel, Forand A, Hebras A, Natalia Prevarskaya, Christian Duhem, Yasmine Sebti, Steve Lancel, Bart Staels, Justine Beauchamp, Hélène Duez, Couvelaere M, Matías Giménez, and Christel Gentil

Subjects
Calcium metabolism, SERCA, Chemistry, Duchenne muscular dystrophy, chemistry.chemical_element, Skeletal muscle, Calcium, medicine.disease, Cell biology, medicine.anatomical_structure, Nuclear receptor, medicine, Myocyte, medicine.symptom, Myopathy
Abstract

The sarcoplasmic reticulum (SR) plays an important role in calcium homeostasis. SR calcium mishandling is described in pathological conditions such as myopathies. Here, we investigated whether the nuclear receptor Rev-erb-α regulates skeletal muscle SR calcium homeostasis. Our data demonstrate that Rev-erbα invalidation in mice impairs SERCA-dependent SR calcium uptake. Rev-erb-α acts on calcium homeostasis by repressing the SERCA inhibitor Myoregulin, through direct binding to its promoter. Restoration of Myoregulin counteracts the effects of REV-ERB-α overexpression on SR calcium content. Interestingly, myoblasts from Duchenne myopathy patients display downregulated REV-ERBα expression, whereas pharmacological Rev-erb activation ameliorates SR calcium homeostasis, and improves muscle structure and function in dystrophic mdx/Utr+/- mice. Our findings demonstrate that Rev-erb-α regulates muscle SR calcium homeostasis, pointing to its therapeutic interest for mitigating myopathy.

Published
2021

23. Uncovering the Role of Glycogen in Brown Adipose Tissue

Author

Alicia Mayeuf-Louchart, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Derudas, Marie-Hélène, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio], Glycogenolysis, Cold exposure, cold exposure, Pharmaceutical Science, lipid droplet, Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Adipose Tissue, Brown, Lipid droplet, Brown adipose tissue, Adipocytes, medicine, Animals, Humans, Lipolysis, Pharmacology (medical), Triglycerides, 030304 developmental biology, Pharmacology, 0303 health sciences, Glycogen, Glycophagy, Organic Chemistry, glycophagy, Thermogenesis, Embryo, brown adipose tissue, Lipid Droplets, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, chemistry, glycogen, lipolysis, Molecular Medicine, Energy Metabolism, 030217 neurology & neurosurgery, Biogenesis, Biotechnology
Abstract

The presence of glycogen in the brown adipose tissue (BAT) has been described 60 years ago. However, the role of this energetic storage in brown adipocytes has been long time underestimated. We have recently shown that during brown adipocyte differentiation in the embryo, glycogen accumulates and is degraded by glycophagy, a dynamic essential for lipid droplets biogenesis. Recent studies have shown that the storage and degradation of triglycerides in BAT are not essential for the activation of BAT in response to cold exposure in adults, and that glycogen can compensate for their absence. In this review, we report the recent advances related to the importance of glycogen in brown adipocytes.

Published
2021

24. [The muscle biological clock]

Author

Mayeuf-Louchart, Alicia, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
Sarcopenia, [SDV]Life Sciences [q-bio], Circadian Clocks, Animals, Humans, Regeneration, Energy Metabolism, Muscle, Skeletal, Exercise, Glucocorticoids, Circadian Rhythm
Abstract

The biological clock plays an essential role in the control of muscle activity, by dissociating temporally the metabolic functions of skeletal muscle. Exercise capacity also displays a circadian rhythm. Alterations in biological rhythm, as in shift workers, alter muscle function and are associated with the development of sarcopenia.L'horloge biologique du muscle.L’horloge biologique joue un rôle essentiel dans le contrôle de l’activité musculaire, en dissociant temporellement les fonctions métaboliques du muscle squelettique. Les capacités musculaires en réponse à l’exercice sont également circadiennes. Des perturbations des rythmes biologiques, telles que celles retrouvées chez les travailleurs postés affectent la fonction musculaire et sont associées au développement de la sarcopénie.

Published
2021

25. [The muscle biological clock]

Author

Alicia Mayeuf-Louchart, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Derudas, Marie-Hélène, and Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD)

Subjects
0301 basic medicine, business.industry, Biological clock, [SDV]Life Sciences [q-bio], Skeletal muscle, General Medicine, Exercise capacity, medicine.disease, General Biochemistry, Genetics and Molecular Biology, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Rhythm, medicine.anatomical_structure, Sarcopenia, medicine, Circadian rhythm, Muscle activity, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

L’horloge biologique joue un rôle essentiel dans le contrôle de l’activité musculaire, en dissociant temporellement les fonctions métaboliques du muscle squelettique. Les capacités musculaires en réponse à l’exercice sont également circadiennes. Des perturbations des rythmes biologiques, telles que celles retrouvées chez les travailleurs postés affectent la fonction musculaire et sont associées au développement de la sarcopénie.

Published
2020

27. Itm2a is a Pax3 target gene, expressed at sites of skeletal muscle formation in vivo.

Author

Mounia Lagha, Alicia Mayeuf-Louchart, Ted Chang, Didier Montarras, Didier Rocancourt, Antoine Zalc, Jay Kormish, Kenneth S Zaret, Margaret E Buckingham, and Frederic Relaix

Subjects
Medicine, Science
Abstract

The paired-box homeodomain transcription factor Pax3 is a key regulator of the nervous system, neural crest and skeletal muscle development. Despite the important role of this transcription factor, very few direct target genes have been characterized. We show that Itm2a, which encodes a type 2 transmembrane protein, is a direct Pax3 target in vivo, by combining genetic approaches and in vivo chromatin immunoprecipitation assays. We have generated a conditional mutant allele for Itm2a, which is an imprinted gene, by flanking exons 2-4 with loxP sites and inserting an IRESnLacZ reporter in the 3' UTR of the gene. The LacZ reporter reproduces the expression profile of Itm2a, and allowed us to further characterize its expression at sites of myogenesis, in the dermomyotome and myotome of somites, and in limb buds, in the mouse embryo. We further show that Itm2a is not only expressed in adult muscle fibres but also in the satellite cells responsible for regeneration. Itm2a mutant mice are viable and fertile with no overt phenotype during skeletal muscle formation or regeneration. Potential compensatory mechanisms are discussed.

Published
2013
Full Text
View/download PDF

28. Rev-erb-α controls skeletal muscle calcium homeostasis through myoregulin repression: implications in Duchenne Muscular Dystrophy

Author

Boulinguiez, Alexis, primary, Duhem, Christian, additional, Mayeuf-Louchart, Alicia, additional, Pourcet, Benoit, additional, Sebti, Yasmine, additional, Kondratska, Kateryna, additional, Montel, Valérie, additional, Delhaye, Stéphane, additional, Thorel, Quentin, additional, Beauchamp, Justine, additional, Hebras, Aurore, additional, Gimenez, Marion, additional, Couvelaere, Marie, additional, Zecchin, Mathilde, additional, Ferri, Lise, additional, Prevarskaya, Natalia, additional, Forand, Anne, additional, Gentil, Christel, additional, Piétri-Rouxel, France, additional, Bastide, Bruno, additional, Staels, Bart, additional, Duez, Helene, additional, and Lancel, Steve, additional

Published
2021
Full Text
View/download PDF

29. Du glycogène à la gouttelette lipidique

Author

Alicia Mayeuf-Louchart, Hélène Duez, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
0303 health sciences, Glycogen, Brown Adipocytes, Cellular differentiation, [SDV]Life Sciences [q-bio], Glycogen metabolism, Adipose tissue, General Medicine, General Biochemistry, Genetics and Molecular Biology, Connection (mathematics), Cell biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Lipid droplet, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience; No abstract available

Published
2020

30. Du glycogène à la gouttelette lipidique: Une intime connexion dans l’adipocyte brun

Author

Mayeuf-Louchart, Alicia, Duez, Hélène, Sciences, EDP, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience; No abstract available

Published
2020

31. Circadian control of metabolism and pathological consequences of clock perturbations

Author

Alicia Mayeuf-Louchart, Mathilde Zecchin, Hélène Duez, Bart Staels, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Derudas, Marie-Hélène

Subjects
0301 basic medicine, medicine.medical_specialty, Adipose tissue, Skeletal muscle, Biology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Circadian Clocks, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, Circadian rhythms, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Nutritional Physiological Phenomena, Obesity, Circadian rhythm, Life Style, Pathological, 2. Zero hunger, Diabetes, Lipid metabolism, General Medicine, Metabolism, medicine.disease, Biological clock, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Liver, Insulin Resistance, Energy Metabolism, 030217 neurology & neurosurgery, Homeostasis
Abstract

International audience; Most organisms have developed an autonomous time-keeping system that generates self-sustained daily fluctuations in behavior and physiological processes. These biological clocks are reset every day by light to adjust physiology to the day/night cycle generated by the rotation of the Earth. Clocks present in organs involved in glucose and lipid metabolism such as the liver, muscle, adipose tissue and pancreas are also reset by feeding cues which permits the local integration of systemic and nutritional signals to switch fuel production and utilization according to the feeding/fasting cycle. However, derangements in this finely tuned system can be induced by extending light exposure, 24/7 food availability and altered food intake patterns, repeated jet-lag and shift-working, promoting metabolic imbalances ranging from body weight gain to the development of insulin resistance and liver diseases. Here, we review recent findings on the link between the clock and metabolic fluxes to maintain whole-body homeostasis, and what clock disruption in mice has revealed about the role of the clock in metabolic regulation.

Published
2017

33. Glycogen Dynamics Drives Lipid Droplet Biogenesis during Brown Adipocyte Differentiation

Author

Mayeuf-Louchart, Alicia, Lancel, Steve, Sebti, Yasmine, Pourcet, Benoit, Loyens, Anne, Delhaye, Stephane, Duhem, Christian, Beauchamp, Justine, Ferri, Lise, Thorel, Quentin, Boulinguiez, Alexis, Zecchin, Mathilde, Dubois-Chevalier, Julie, Eeckhoute, Jerome, Vaughn, Logan, Roach, Peter, Dani, Christian, Pederson, Bartholomew, Vincent, Stéphane, Staels, Bart, Duez, Hélène, Derudas, Marie-Hélène, EGID Diabetes Pole - - EGID2010 - ANR-10-LABX-0046 - LABX - VALID, Bile acid, immune-metabolism, lipid and glucose homeostasis - ImmunoBile - - H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) 2016-09-01 - 2021-08-31 - 694717 - VALID, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Indiana University School of Medicine-Muncie [Muncie, IN, USA], Ball State University, Department of Biochemistry and Molecular Biology [Indianapolis, IN, USA], Indiana University School of Medicine, Indiana University System-Indiana University System, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), We acknowledge the support from INSERM, the ANR-Labex-EGID (EGID, ANR-10-LABX-46), the Fondation Francophone pour la recherche sur le diabète (FFRD) together with the Fédération Française des Diabétiques (AFD) AstraZeneca, Eli Lilly, Merck Sharp & Dohme (MSD), Novo Nordisk & Sanofi, the Région Hauts-de-France/FEDER (Chronoregeneration) and Fondation de France. A.M-L. was supported by the Association Française contre les Myopathies (AFM-Téléthon). B.S is a recipient of an Advanced ERC Grant (694717). B.A.P was supported by National Institutes of Health funding (DK078370) and P.J.R by National Institutes of Health funding (DK27221)., ANR-10-LABX-0046,EGID,EGID Diabetes Pole(2010), European Project: 694717,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ImmunoBile(2016), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
autophagy, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Fatty Acid-Binding Proteins, Article, Mice, Adipose Tissue, Brown, Microscopy, Electron, Transmission, lipid, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Animals, Humans, RNA, Small Interfering, lcsh:QH301-705.5, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Cells, Cultured, adipocyte differentiation, Adipogenesis, glycophagy, lipid droplet biogenesis, BAT, brown adipose tissue, Lipid Droplets, Embryo, Mammalian, Mice, Inbred C57BL, PPAR gamma, Adipocytes, Brown, lcsh:Biology (General), glycogen, embryonic development, adipocyte metabolism, CCAAT-Enhancer-Binding Proteins, Transcriptome
Abstract

Summary Browning induction or transplantation of brown adipose tissue (BAT) or brown/beige adipocytes derived from progenitor or induced pluripotent stem cells (iPSCs) can represent a powerful strategy to treat metabolic diseases. However, our poor understanding of the mechanisms that govern the differentiation and activation of brown adipocytes limits the development of such therapy. Various genetic factors controlling the differentiation of brown adipocytes have been identified, although most studies have been performed using in vitro cultured pre-adipocytes. We investigate here the differentiation of brown adipocytes from adipose progenitors in the mouse embryo. We demonstrate that the formation of multiple lipid droplets (LDs) is initiated within clusters of glycogen, which is degraded through glycophagy to provide the metabolic substrates essential for de novo lipogenesis and LD formation. Therefore, this study uncovers the role of glycogen in the generation of LDs., Graphical Abstract, Highlights • Brown adipocytes are functionally differentiated at E17.5 in the mouse embryo • Lipid droplets are formed within glycogen clusters • Glycogen production is crucial for lipid droplet biogenesis during BAT differentiation • Glycophagy-mediated glycogen degradation drives lipid droplet formation, Lipid droplet formation is a major feature of brown adipocyte differentiation. Mayeuf-Louchart et al. characterize the different steps of brown adipocyte differentiation in the mouse embryo and report the essential role of glycogen production and degradation by glycophagy for lipid droplet biogenesis.

Published
2019

34. MuscleJ: a high-content analysis method to study skeletal muscle with a new Fiji tool

Author

Hélène Duez, Adrien Bouglé, David Briand, Pascal Roux, Bart Staels, Lorna Guéniot, Anne Danckaert, Spencer L. Shorte, Alicia Mayeuf-Louchart, Quentin Thorel, Fabrice Chrétien, David Hardy, Aurélien Mazeraud, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Neuropathologie expérimentale - Experimental neuropathology, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 (UPD5), Institut Pasteur [Paris], BioImagerie Photonique – Photonic BioImaging (UTechS PBI), This work was supported by research grants from the Association Française contre les Myopathies AFM (to AML, FC and DH), Fédération Francophone de Recherche sur le Diabète FFRD, sponsored by Fédération Française des Diabétiques (AFD), AstraZeneca, Eli Lilly, Merck Sharp & Dohme (MSD), Novo Nordisk & Sanofi, (to HD), Fondation de France (to HD), the 'European Genomic Institute for Diabetes' (EGID, ANR-10-LABX-46) (to HD and BS), the Fondation des Gueules Cassées (DH and FC), and an ERC-Région Hauts de France funding (to HD). BS is a holder of an ERC advanced grant no. 694717 'Bile acid, immune-metabolism, lipid and glucose homeostasis'. The PBI (AD, PR, and SLS) is part of the France BioImaging infrastructure supported by the French National Research Agency (ANR-10-INSB-04-01, 'Investments for the future'), ANR-10-LABX-0046,EGID,EGID Diabetes Pole(2010), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), European Project: 694717,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ImmunoBile(2016), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Technologie et Service BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris]-Institut Pasteur [Paris], ANR-10-LABX-0046/10-LABX-0046,EGID,EGID Diabetes Pole(2010), ANR-10-INBS-04-01/10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Institut Pasteur [Paris] (IP)-Université Paris Descartes - Paris 5 (UPD5), and Institut Pasteur [Paris] (IP)

Subjects
0301 basic medicine, lcsh:Diseases of the musculoskeletal system, Histology, Computer science, Muscle Fibers, Skeletal, Stem cells, In situ cartography, 03 medical and health sciences, Mice, Software, Satellite cells, medicine, Image Processing, Computer-Assisted, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Orthopedics and Sports Medicine, Segmentation, Statistical analysis, Muscle fibre, Molecular Biology, business.industry, Optical Imaging, Methodology, Skeletal muscle, Cell Biology, Skeletal muscle fiber, 030104 developmental biology, medicine.anatomical_structure, Open source, Fiber typing, Image automated quantification, Vessels, Experimental methods, lcsh:RC925-935, business, Biomedical engineering, Muscle physiology
Abstract

Background Skeletal muscle has the capacity to adapt to environmental changes and regenerate upon injury. To study these processes, most experimental methods use quantification of parameters obtained from images of immunostained skeletal muscle. Muscle cross-sectional area, fiber typing, localization of nuclei within the muscle fiber, the number of vessels, and fiber-associated stem cells are used to assess muscle physiology. Manual quantification of these parameters is time consuming and only poorly reproducible. While current state-of-the-art software tools are unable to analyze all these parameters simultaneously, we have developed MuscleJ, a new bioinformatics tool to do so. Methods Running on the popular open source Fiji software platform, MuscleJ simultaneously analyzes parameters from immunofluorescent staining, imaged by different acquisition systems in a completely automated manner. Results After segmentation of muscle fibers, up to three other channels can be analyzed simultaneously. Dialog boxes make MuscleJ easy-to-use for biologists. In addition, we have implemented color in situ cartographies of results, allowing the user to directly visualize results on reconstituted muscle sections. Conclusion We report here that MuscleJ results were comparable to manual observations made by five experts. MuscleJ markedly enhances statistical analysis by allowing reliable comparison of skeletal muscle physiology-pathology results obtained from different laboratories using different acquisition systems. Providing fast robust multi-parameter analyses of skeletal muscle physiology-pathology, MuscleJ is available as a free tool for the skeletal muscle community. Electronic supplementary material The online version of this article (10.1186/s13395-018-0171-0) contains supplementary material, which is available to authorized users.

Published
2018

35. Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity

Author

Lancel, S. (Steve), Hesselink, M.K. (Matthijs Kc), Woldt, E. (Estelle), Rouille, Y. (Yves), Dorchies, E. (Emilie), Delhaye, S. (Stephane), Duhem, C. (Christian), Thorel, Q. (Quentin), Mayeuf-Louchart, A. (Alicia), Pourcet, B. (Benoit), Montel, V. (Valerie), Schaart, G. (Gert), Beton, N. (Nicolas), Picquet, F. (Florence), Briand, O. (Olivier), Salles, J.P. (Jean Pierre), Duez, H. (Helene), Schrauwen, P. (Patrick), Bastide, B. (Bruno), Bailleul, B. (Bernard), Staels, B. (Bart), Sebti, Y. (Yasmine), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maastricht University [Maastricht], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 (URePSSS), Université d'Artois (UA)-Université de Lille-Université du Littoral Côte d'Opale (ULCO), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Project: 694717,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ImmunoBile(2016), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Maastricht University Medical Center (MUMC), Centre d’Infection et d’Immunité de Lille (CIIL) - INSERM U1019 - UMR 9017 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - EA 7369 (URePSSS), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Université d'Artois (UA), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), This research was supported by the European Genomic Institute for Diabetes (EGID, ANR-10-LABX-46) and European Commission, Lille Métropole Communauté Urbaine (to YS), Région Nord Pas-de-Calais/FEDER (to BS), CPER 2011-R3-P12A (to B. Bailleul), a joint Société Francophone du Diabète (SFD)/Menarini research fellowship (to B. Bailleul), EFSD/Lilly research grant and CPER emerging team (to HD), Eurhythdia (to BS and HD), ERC Région Haut de France (to HD), and Pfizer France and Ipsen Beaufour (to JPS). BS hold an ERC advanced grant (no. 694717)., ANR-10-LABX-0046/10-LABX-0046,EGID,EGID Diabetes Pole(2010), Nutrition and Movement Sciences, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, Ondersteunend personeel NTM, Université de Lille, Univ. Artois, Univ. Littoral Côte d’Opale, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 [URePSSS], and Centre de Physiopathologie Toulouse Purpan [CPTP]

Subjects
Male, [SDV]Life Sciences [q-bio], Cell Plasticity, Messenger, Skeletal muscle, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MOUSE, STAT3, Mice, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, Glucose metabolism, Cultured, ACTIVATED PROTEIN-KINASE, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, MITOCHONDRIAL BIOGENESIS, Skeletal, Mitochondria, ERK, Muscle Fibers, Slow-Twitch, Phenotype, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Muscle Fibers, Fast-Twitch, Muscle, Female, PHENOTYPIC ANALYSIS, Research Article, PERMEABILITY TRANSITION, MAP Kinase Signaling System, Cells, Physical Exertion, EXERCISE, Slow-Twitch, Muscle Fibers, Signal Transducing, Animals, Autophagy, Caloric Restriction, Energy Metabolism, Humans, Membrane Proteins, Fast-Twitch, Oxidative Stress, Physical Endurance, RNA, Metabolism, Muscle Biology, RNA, Messenger, Muscle, Skeletal, Adaptor Proteins, Signal Transducing, ELECTRON-TRANSPORT CHAIN
Abstract

International audience; Metabolic stresses such as dietary energy restriction or physical activity exert beneficial metabolic effects. In the liver, endospanin-1 and endospanin-2 cooperatively modulate calorie restriction-mediated (CR-mediated) liver adaptations by controlling growth hormone sensitivity. Since we found CR to induce endospanin protein expression in skeletal muscle, we investigated their role in this tissue. In vivo and in vitro endospanin-2 triggers ERK phosphorylation in skeletal muscle through an autophagy-dependent pathway. Furthermore, endospanin-2, but not endospanin-1, overexpression decreases muscle mitochondrial ROS production, induces fast-to-slow fiber-type switch, increases skeletal muscle glycogen content, and improves glucose homeostasis, ultimately promoting running endurance capacity. In line, endospanin-2-/- mice display higher lipid peroxidation levels, increased mitochondrial ROS production under mitochondrial stress, decreased ERK phosphorylation, and reduced endurance capacity. In conclusion, our results identify endospanin-2 as a potentially novel player in skeletal muscle metabolism, plasticity, and function.

Published
2018

36. Additional file 1: of MuscleJ: a high-content analysis method to study skeletal muscle with a new Fiji tool

Author

Mayeuf-Louchart, Alicia, Hardy, David, Thorel, Quentin, Roux, Pascal, Gueniot, Lorna, Briand, David, Mazeraud, Aurélien, Bouglé, Adrien, Shorte, Spencer, Staels, Bart, Chrétien, Fabrice, Duez, Hélène, and Danckaert, Anne

Subjects
GeneralLiterature_INTRODUCTORYANDSURVEY, ComputingMilieux_COMPUTERSANDEDUCATION, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, ComputerApplications_COMPUTERSINOTHERSYSTEMS
Abstract

Supplementary tables, figures and tutorial. (PDF 2355 kb)

Published
2018
Full Text
View/download PDF

37. Skeletal muscle functions around the clock

Author

Alicia Mayeuf-Louchart, Hélène Duez, and Bart Staels

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Central nervous system, Circadian clock, Clockwork, Biology, Muscle Development, Eating, Endocrinology, Circadian Clocks, Internal medicine, Internal Medicine, medicine, Animals, Humans, Circadian rhythm, Muscle, Skeletal, Molecular clock, Exercise, Transcription factor, Myogenesis, Skeletal muscle, Circadian Rhythm, medicine.anatomical_structure, Neuroscience, Transcription Factors
Abstract

In mammals, the central clock localized in the central nervous system imposes a circadian rhythmicity to all organs. This is achieved thanks to a well-conserved molecular clockwork, involving interactions between several transcription factors, whose pace is conveyed to peripheral tissues through neuronal and humoral signals. The molecular clock plays a key role in the control of numerous physiological processes and takes part in the regulation of metabolism and energy balance. Skeletal muscle is one of the peripheral organs whose function is under the control of the molecular clock. However, although skeletal muscle metabolism and performances display circadian rhythmicity, the role of the molecular clock in the skeletal muscle has remained unappreciated for years. Peripheral organs such as skeletal muscle, and the liver, among others, can be desynchronized from the central clock by external stimuli, such as feeding or exercise, which impose a new rhythm at the organism level. In this review, we discuss our current understanding of the clock in skeletal muscle circadian physiology, focusing on the control of myogenesis and skeletal muscle metabolism.

Published
2015

38. Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity

Author

Lancel, Steve, Lancel, Steve, Hesselink, Matthijs K. C., Woldt, Estelle, Rouille, Yves, Dorchies, Emilie, Delhaye, Stephane, Duhem, Christian, Thorel, Quentin, Mayeuf-Louchart, Alicia, Pourcet, Benoit, Montel, Valerie, Schaart, Gert, Beton, Nicolas, Picquet, Florence, Briand, Olivier, Salles, Jean Pierre, Duez, Helene, Schrauwen, Patrick, Bastide, Bruno, Bailleul, Bernard, Staels, Bart, Sebti, Yasmine, Lancel, Steve, Lancel, Steve, Hesselink, Matthijs K. C., Woldt, Estelle, Rouille, Yves, Dorchies, Emilie, Delhaye, Stephane, Duhem, Christian, Thorel, Quentin, Mayeuf-Louchart, Alicia, Pourcet, Benoit, Montel, Valerie, Schaart, Gert, Beton, Nicolas, Picquet, Florence, Briand, Olivier, Salles, Jean Pierre, Duez, Helene, Schrauwen, Patrick, Bastide, Bruno, Bailleul, Bernard, Staels, Bart, and Sebti, Yasmine

Abstract

Metabolic stresses such as dietary energy restriction or physical activity exert beneficial metabolic effects. In the liver, endospanin-1 and endospanin-2 cooperatively modulate calorie restriction-mediated (CR-mediated) liver adaptations by controlling growth hormone sensitivity. Since we found CR to induce endospanin protein expression in skeletal muscle, we investigated their role in this tissue. In vivo and in vitro endospanin-2 triggers ERK phosphorylation in skeletal muscle through an autophagy-dependent pathway. Furthermore, endospanin-2, but not endospanin-1, overexpression decreases muscle mitochondrial ROS production, induces fast-to-slow fiber-type switch, increases skeletal muscle glycogen content, and improves glucose homeostasis, ultimately promoting running endurance capacity. In line, endospanin-2(-/-) mice display higher lipid peroxidation levels, increased mitochondrial ROS production under mitochondrial stress, decreased ERK phosphorylation, and reduced endurance capacity. In conclusion, our results identify endospanin-2 as a potentially novel player in skeletal muscle metabolism, plasticity, and function.

Published
2018

39. Rev-erb-α regulates atrophy-related genes to control skeletal muscle mass

Author

Alicia Mayeuf-Louchart, Quentin Thorel, Stéphane Delhaye, Justine Beauchamp, Christian Duhem, Anne Danckaert, Steve Lancel, Benoit Pourcet, Estelle Woldt, Alexis Boulinguiez, Lise Ferri, Mathilde Zecchin, Bart Staels, Yasmine Sebti, and Hélène Duez

Subjects
Mice, Knockout, Transcriptional Activation, Adipogenesis, viruses, lcsh:R, lcsh:Medicine, Cell Differentiation, Article, body regions, Repressor Proteins, Mice, Muscular Atrophy, Liver, Muscular Diseases, Nuclear Receptor Subfamily 1, Group D, Member 1, Autophagy, Animals, lcsh:Q, lcsh:Science, skin and connective tissue diseases, Muscle, Skeletal
Abstract

The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and thermogenesis. We have previously demonstrated that Rev-erb-α is also an important regulator of skeletal muscle mitochondrial biogenesis and function, and autophagy. As such, Rev-erb-α over-expression in skeletal muscle or its pharmacological activation improved mitochondrial respiration and enhanced exercise capacity. Here, in gain- and loss-of function studies, we show that Rev-erb-α also controls muscle mass. Rev-erb-α-deficiency in skeletal muscle leads to increased expression of the atrophy-related genes (atrogenes), associated with reduced muscle mass and decreased fiber size. By contrast, in vivo and in vitro Rev-erb-α over-expression results in reduced atrogenes expression and increased fiber size. Finally, Rev-erb-α pharmacological activation blocks dexamethasone-induced upregulation of atrogenes and muscle atrophy. This study identifies Rev-erb-α as a promising pharmacological target to preserve muscle mass.

Published
2017

41. Endothelial cell specification in the somite is compromised in Pax3-positive progenitors of Foxc1/2 conditional mutants, with loss of forelimb myogenesis

Author

Alicia Mayeuf-Louchart, Catherine Bodin, Didier Montarras, Stéphane D. Vincent, Tsutomu Kume, Margaret Buckingham, Département de Biologie du Développement et Cellules souches - Department of Developmental and Stem Cell Biology, Institut Pasteur [Paris] (IP), Biologie du Développement et Cellules souches (CNRS UMR3738), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, This work was supported by a PhD fellowship awarded by the Université Paris VI (A.M.L.), the Association Française contre les Myopathies (A.M.L.), OptiStem [grants 223098 to A.M.L. and 223098 to M.B.], the Pasteur Institute (M.B. and D.M.), the Centre National de la Recherche Scientifique (M.B. and D.M.), the French Association against Myopathies (AFM) [12761/13866 to M.B.], the European Union framework programmes EuroSystem [grant 200720 to M.B.], the Laboratoire d'Excellence Revive [Investissement d'Avenir, ANR-10-LABX-73 to M.B. and D.M.], and the National Institutes of Health [EY019484 and HL074121 to T.K.]. Deposited in PMC for release after 12 months., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), European Project: 200720,EC:FP7:HEALTH,FP7-HEALTH-2007-A,EUROSYSTEM(2008), Institut Pasteur [Paris], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), VINCENT, Stéphane, Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID, and European Consortium for Systematic Stem Cell Biology - EUROSYSTEM - - EC:FP7:HEALTH2008-03-01 - 2012-08-31 - 200720 - VALID

Subjects
Male, 0301 basic medicine, Muscle Proteins, Cell Separation, Muscle Development, Mice, Cell Movement, Genes, Reporter, Somitogenesis, Forelimb, Paired Box Transcription Factors, In Situ Hybridization, ComputingMilieux_MISCELLANEOUS, Genetics, education.field_of_study, Myogenesis, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Gene Expression Regulation, Developmental, Forkhead Transcription Factors, Flow Cytometry, Cell biology, Endothelial stem cell, Phenotype, medicine.anatomical_structure, Somites, Female, Research Article, Limb Buds, Population, Mice, Transgenic, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, Biology, Cell fate determination, 03 medical and health sciences, Limb bud, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, PAX3 Transcription Factor, Molecular Biology, Crosses, Genetic, Endothelial Cells, Somite, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Mutation, Developmental Biology
Abstract

International audience; Pax3 and Foxc2 have been shown genetically to mutually repress each other in the mouse somite. Perturbation of this balance in multipotent cells of the dermomyotome influences cell fate; upregulation of Foxc2 favours a vascular fate, whereas higher levels of Pax3 lead to myogenesis. Foxc1 has overlapping functions with Foxc2. In Foxc1/2 double-mutant embryos, somitogenesis is severely affected, precluding analysis of somite derivatives. We have adopted a conditional approach whereby mutations in Foxc1 and Foxc2 genes were targeted to Pax3-expressing cells. Inclusion of a conditional reporter allele in the crosses made it possible to follow cells that had expressed Pax3. At the forelimb level, endothelial and myogenic cells migrate from adjacent somites into the limb bud. This population of endothelial cells is compromised in the double mutant, whereas excessive production of myogenic cells is observed in the trunk. However, strikingly, myogenic progenitors fail to enter the limbs, leading to the absence of skeletal muscle. Pax3-positive migratory myogenic progenitors, marked by expression of Lbx1, are specified in the somite at forelimb level, but endothelial progenitors are absent. The myogenic progenitors do not die, but differentiate prematurely adjacent to the somite. We conclude that the small proportion of somite-derived endothelial cells in the limb is required for the migration of myogenic limb progenitors.

Published
2016

42. Rev-erb-α regulates atrophy-related genes to control skeletal muscle mass

Author

Mayeuf-Louchart, Alicia, primary, Thorel, Quentin, additional, Delhaye, Stéphane, additional, Beauchamp, Justine, additional, Duhem, Christian, additional, Danckaert, Anne, additional, Lancel, Steve, additional, Pourcet, Benoit, additional, Woldt, Estelle, additional, Boulinguiez, Alexis, additional, Ferri, Lise, additional, Zecchin, Mathilde, additional, Staels, Bart, additional, Sebti, Yasmine, additional, and Duez, Hélène, additional

Published
2017
Full Text
View/download PDF

45. Prdm1 functions in the mesoderm of the second heart field, where it interacts genetically with Tbx1, during outflow tract morphogenesis in the mouse embryo

Author

Sachiko Miyagawa-Tomita, Joseph A. Brzezinski, Margaret Buckingham, Alicia Mayeuf-Louchart, Robert G. Kelly, Yusuke Watanabe, Stéphane D. Vincent, Département de Biologie du Développement et Cellules souches - Department of Developmental and Stem Cell Biology, Institut Pasteur [Paris] (IP), Bases Génétiques, Moléculaires et Cellulaires du Développement (BGMCD), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Washington [Seattle], Tokyo Women's Medical University (TWMU), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Institut Pasteur and the CNRS URA 2578 (National Centre for Scientific Research), with grants from the E.U. Integrated Project ‘Heart Repair’ (LHSM-CT2005-018630) and ‘CardioCell’ (LT2009-223372) to M.B. S.M.-T. received a fellowship from the Naito foundation., European Project: 32570,HEARTREPAIR, European Project: 223372,EC:FP7:HEALTH,FP7-HEALTH-2007-B,CARDIOCELL(2009), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Department of Structural Biology [Seattle], Department of Pediatric Cardiology [Tokyo], Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), VINCENT, Stéphane, Heart Failure and Repair - HEARTREPAIR - 32570 - OLD, and Development of cardiomyocyte replacement strategy for the clinic - CARDIOCELL - - EC:FP7:HEALTH2009-05-01 - 2012-10-31 - 223372 - VALID

Subjects
Male, Pathology, Organogenesis, Gene Expression, Aorta, Thoracic, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Mesoderm, Gene Knockout Techniques, Mice, hemic and lymphatic diseases, Morphogenesis, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Heart development, Stem Cells, Neural crest, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Gene Expression Regulation, Developmental, Heart, General Medicine, Anatomy, Arterial tree, medicine.anatomical_structure, embryonic structures, Female, medicine.medical_specialty, Genotype, Persistent truncus arteriosus, Mice, Transgenic, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, medicine.artery, Genetics, medicine, Animals, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Aorta, Lateral plate mesoderm, Epistasis, Genetic, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Embryo, Mammalian, Outflow tract morphogenesis, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Branchial Region, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Mutation, Positive Regulatory Domain I-Binding Factor 1, T-Box Domain Proteins, Pharyngeal arch, Transcription Factors
Abstract

International audience; Congenital heart defects affect at least 0.8% of newborn children and are a major cause of lethality prior to birth. Malformations of the arterial pole are particularly frequent. The myocardium at the base of the pulmonary trunk and aorta and the arterial tree associated with these great arteries are derived from splanchnic mesoderm of the second heart field (SHF), an important source of cardiac progenitor cells. These cells are controlled by a gene regulatory network that includes Fgf8, Fgf10 and Tbx1. Prdm1 encodes a transcriptional repressor that we show is also expressed in the SHF. In mouse embryos, mutation of Prdm1 affects branchial arch development and leads to persistent truncus arteriosus (PTA), indicative of neural crest dysfunction. Using conditional mutants, we show that this is not due to a direct function of Prdm1 in neural crest cells. Mutation of Prdm1 in the SHF does not result in PTA, but leads to arterial pole defects, characterized by mis-alignment or reduction of the aorta and pulmonary trunk, and abnormalities in the arterial tree, defects that are preceded by a reduction in outflow tract size and loss of caudal pharyngeal arch arteries. These defects are associated with a reduction in proliferation of progenitor cells in the SHF. We have investigated genetic interactions with Fgf8 and Tbx1, and show that on a Tbx1 heterozygote background, conditional Prdm1 mutants have more pronounced arterial pole defects, now including PTA. Our results identify PRDM1 as a potential modifier of phenotypic severity in TBX1 haploinsufficient DiGeorge syndrome patients.

Published
2014

46. Notch regulation of myogenic versus endothelial fates of cells that migrate from the somite to the limb

Author

Anne Danckaert, Didier Rocancourt, Frédéric Relaix, Alicia Mayeuf-Louchart, Stéphane D. Vincent, Mounia Lagha, Margaret Buckingham, Bases Génétiques, Moléculaires et Cellulaires du Développement (BGMCD), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Imagerie Dynamique (Plate-Forme) (PFID), Institut Pasteur [Paris] (IP), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Biologie du Développement et Cellules souches - Department of Developmental and Stem Cell Biology, Institut Pasteur [Paris], and VINCENT, Stéphane

Subjects
Male, Cellular differentiation, Genetic Vectors, PAX3, Notch signaling pathway, Mice, Transgenic, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, Biology, Muscle Development, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Mice, Skeletal muscle cell differentiation, Cell Movement, medicine, Animals, Paired Box Transcription Factors, Cell Lineage, Progenitor cell, Muscle, Skeletal, PAX3 Transcription Factor, Alleles, Multidisciplinary, Receptors, Notch, Endothelial Cells, Gene Expression Regulation, Developmental, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Skeletal muscle, Cell Differentiation, Extremities, Forkhead Transcription Factors, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biological Sciences, musculoskeletal system, Cell biology, Somite, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, medicine.anatomical_structure, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Somites, embryonic structures, Immunology, Female, Signal transduction, Signal Transduction
Abstract

Multipotent Pax3-positive (Pax3(+)) cells in the somites give rise to skeletal muscle and to cells of the vasculature. We had previously proposed that this cell-fate choice depends on the equilibrium between Pax3 and Foxc2 expression. In this study, we report that the Notch pathway promotes vascular versus skeletal muscle cell fates. Overactivating the Notch pathway specifically in Pax3(+) progenitors, via a conditional Pax3(NICD) allele, results in an increase of the number of smooth muscle and endothelial cells contributing to the aorta. At limb level, Pax3(+) cells in the somite give rise to skeletal muscles and to a subpopulation of endothelial cells in blood vessels of the limb. We now demonstrate that in addition to the inhibitory role of Notch signaling on skeletal muscle cell differentiation, the Notch pathway affects the Pax3:Foxc2 balance and promotes the endothelial versus myogenic cell fate, before migration to the limb, in multipotent Pax3(+) cells in the somite of the mouse embryo.

Published
2014

48. Itm2a is a Pax3 target gene, expressed at sites of skeletal muscle formation in vivo

Author

Mounia Lagha, Didier Montarras, Antoine Zalc, Kenneth S. Zaret, Jay D. Kormish, Margaret Buckingham, Alicia Mayeuf-Louchart, Didier Rocancourt, Frédéric Relaix, Ted Hung-Tse Chang, Biologie du Développement, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Groupe Myologie, Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pennsylvania, This project was supported by funding to FR from the INSERM Avenir Program, Association Française Contre les Myopathies (AFM), Association Institut de Myologie, the Ligue Nationale Contre le Cancer (LNCC), Association pour la Recherche Contre le Cancer (ARC), Fondation pour la Recherche Médicale, Institut National du Cancer (INCa), and from the European Union Seventh Framework Programme in the project ENDOSTEM (grant agreement number 241440). MB’s laboratory was supported by the Pasteur Institute and the CNRS (URA 2578) and by grants from the AFM and the EU 7th PCRD programmes, EuroSyStem (grant agreement number 200720) and Optistem (grant agreement number 223098). ML is currently the recipient of a Human Frontier Science Program (HFSP) fellowship., European Project: 241440,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,ENDOSTEM(2010), European Project: 200720,EC:FP7:HEALTH,FP7-HEALTH-2007-A,EUROSYSTEM(2008), European Project: 223098,EC:FP7:HEALTH,FP7-HEALTH-2007-B,OPTISTEM(2009), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pennsylvania [Philadelphia], Adele, Sarah, Activation of vasculature associated stem cells and muscle stem cells for the repair and maintenance of muscle tissue - ENDOSTEM - - EC:FP7:HEALTH2010-01-01 - 2014-12-31 - 241440 - VALID, European Consortium for Systematic Stem Cell Biology - EUROSYSTEM - - EC:FP7:HEALTH2008-03-01 - 2012-08-31 - 200720 - VALID, and Optimization of stem cell therapy for clinical trials of degenerative skin and muscle diseases - OPTISTEM - - EC:FP7:HEALTH2009-01-01 - 2013-12-31 - 223098 - VALID

Subjects
Male, Embryology, Mouse, Mutant, PAX3, lcsh:Medicine, Gene Expression, Muscle Development, Cell Fate Determination, Mice, 0302 clinical medicine, Molecular Cell Biology, Paired Box Transcription Factors, lcsh:Science, 0303 health sciences, Multidisciplinary, Myogenesis, Stem Cells, Gene Expression Regulation, Developmental, Animal Models, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Myogenic Regulatory Factor 5, Research Article, Satellite Cells, Skeletal Muscle, Cre recombinase, Mice, Transgenic, Biology, 03 medical and health sciences, Model Organisms, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Genetics, Animals, Muscle, Skeletal, Transcription factor, PAX3 Transcription Factor, 030304 developmental biology, Cell Nucleus, lcsh:R, Skeletal muscle, Membrane Proteins, Molecular biology, Mice, Inbred C57BL, lcsh:Q, Genomic imprinting, Chromatin immunoprecipitation, Organism Development, Animal Genetics, Developmental Biology
Abstract

International audience; The paired-box homeodomain transcription factor Pax3 is a key regulator of the nervous system, neural crest and skeletal muscle development. Despite the important role of this transcription factor, very few direct target genes have been characterized. We show that Itm2a, which encodes a type 2 transmembrane protein, is a direct Pax3 target in vivo, by combining genetic approaches and in vivo chromatin immunoprecipitation assays. We have generated a conditional mutant allele for Itm2a, which is an imprinted gene, by flanking exons 2-4 with loxP sites and inserting an IRESnLacZ reporter in the 3' UTR of the gene. The LacZ reporter reproduces the expression profile of Itm2a, and allowed us to further characterize its expression at sites of myogenesis, in the dermomyotome and myotome of somites, and in limb buds, in the mouse embryo. We further show that Itm2a is not only expressed in adult muscle fibres but also in the satellite cells responsible for regeneration. Itm2a mutant mice are viable and fertile with no overt phenotype during skeletal muscle formation or regeneration. Potential compensatory mechanisms are discussed.

Published
2012

Catalog

Books, media, physical & digital resources
See catalog results