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1. Eye morphogenesis in the blind Mexican cavefish

Author

Laurent Legendre, François Agnès, Lucie Devos, Naima El Khallouki, Frédéric Sohm, Victor Simon, Joanne Edouard, Sosthène Barbachou, Sylvie Rétaux, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Animaux Modèles Aquatiques : ingéniérie GENétique (AMAGEN), and Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
genetic structures, QH301-705.5, Science, Morphogenesis, Cavefish, Biology, Optic cup (anatomical), Blindness, Eye, General Biochemistry, Genetics and Molecular Biology, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, biology.animal, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, medicine, Animals, Optic vesicle, Biology (General), Cell behaviours, Live imaging, 030304 developmental biology, 0303 health sciences, Coloboma, Eye morphogenesis, Evo-devo, Fishes, Vertebrate, [SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis, CRISPR/Cas9 knock-in, medicine.disease, eye diseases, 3. Good health, medicine.anatomical_structure, Evolutionary biology, Lens (anatomy), Evolutionary developmental biology, Zic1, Retinal pigmented epithelium, sense organs, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, Research Article
Abstract

The morphogenesis of the vertebrate eye consists of a complex choreography of cell movements, tightly coupled to axial regionalization and cell type specification processes. Disturbances in these events can lead to developmental defects and blindness. Here, we have deciphered the sequence of defective events leading to coloboma in the embryonic eye of the blind cavefish of the species Astyanax mexicanus. Using comparative live imaging on targeted enhancer-trap Zic1:hsp70:GFP reporter lines of both the normal, river-dwelling morph and the cave morph of the species, we identified defects in migratory cell behaviours during evagination that participate in the reduced optic vesicle size in cavefish, without proliferation defect. Further, impaired optic cup invagination shifts the relative position of the lens and contributes to coloboma in cavefish. Based on these results, we propose a developmental scenario to explain the cavefish phenotype and discuss developmental constraints to morphological evolution. The cavefish eye appears as an outstanding natural mutant model to study molecular and cellular processes involved in optic region morphogenesis., Summary: We show that the developing embryonic eye of the blind Mexican cavefish suffers multiple tissue morphogenesis and cell behaviour defects that lead to coloboma.

Published
2021
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2. Fgfr3 Is a Positive Regulator of Osteoblast Expansion and Differentiation During Zebrafish Skull Vault Development

Author

Laurence Legeai-Mallet, Ghaith Abdessalem, Emilie Dambroise, Joanne Edouard, E. Elizabeth Patton, Björn Busse, Olivier Pellé, Frédéric Sohm, Alessandro Brombin, Olivia Binder, Ivan Ktorza, Imke A. K. Fiedler, Marine Luka, Mickaël M. Ménager, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), MRC Human Genetics Unit, University of Edinburgh-Western General Hospital, Cancer Research UK Edinburgh Centre [Edinburgh, UK], University of Edinburgh-MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council-Medical Research Council, Animaux Modèles Aquatiques : ingéniérie GENétique (AMAGEN), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département Plateforme (PF I2BC), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Department of Osteology and Biomechanics, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Inflammasome NLRP3 – NLRP3 Inflammasome, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), French National Research Agency (ANR)ANR-10-EQPX-03ANR10-INBS-09-08European Commission602300UK Research & Innovation (UKRI)Medical Research Council UK (MRC)MC_UU_000007/9European Research Council (ERC)European CommissionZF-MEL-CHEMBIO-648489L'Oreal Melanoma Research Alliance 401181l'Association des Gueules Cassees Region Ile-de-France, Lallemant, Christopher, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-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)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, Endocrinology, Diabetes and Metabolism, Fgfr3, Regulator, Cranial Vault Defects, 030209 endocrinology & metabolism, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, Osteogenesis, Cranial vault, medicine, Animals, Receptor, Fibroblast Growth Factor, Type 3, Orthopedics and Sports Medicine, Zebrafish, 030304 developmental biology, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, Osteoblasts, biology, Skull, Cell Differentiation, Osteoblast, Zebrafish Proteins, Fibroblast growth factor receptor 3, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, biology.organism_classification, Cell biology, stomatognathic diseases, 030104 developmental biology, medicine.anatomical_structure, Intramembranous ossification, 030217 neurology & neurosurgery
Abstract

Gain- or loss-of-function mutations in fibroblast growth factor receptor 3 (FGFR3) result in cranial vault defects - highlighting the protein’s role in membranous ossification. Zebrafish express high levels of fgfr3 during skull development; in order to study FGFR3’s role in cranial vault development, we generated the first fgfr3 loss-of-function zebrafish (fgfr3lof/lof). The mutant fish exhibited major changes in the craniofacial skeleton, with a lack of sutures, abnormal frontal and parietal bones, and the presence of ectopic bones. Integrated analyses (in vivo imaging, and single-cell RNA sequencing of the osteoblast lineage) of zebrafish fgfr3lof/lof revealed a delay in osteoblast expansion and differentiation, together with changes in the extracellular matrix. These findings demonstrate that fgfr3 is a positive regulator of osteogenesis. We hypothesize that changes in the extracellular matrix within growing bone impair cell-cell communication, mineralization, and new osteoblast recruitment.

Published
2020
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3. TRIM8 is required for virus-induced IFN response in human plasmacytoid dendritic cells

Author

Olivier Moncorgé, Sarah Maillet, Jean-Philippe Herbeuval, Nikaïa Smith, Joanne Edouard, Ghizlane Maarifi, Nathalie J. Arhel, Jean-Pierre Levraud, Frédéric Sohm, Georges Lutfalla, Fabien Blanchet, Sébastien Nisole, Célia Chamontin, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Universitätsklinikum Ulm - University Hospital of Ulm, Equipe Chimie et Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5), Animaux Modèles Aquatiques : ingéniérie GENétique (AMAGEN), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Macrophages et Développement de l’Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Funding: This work was supported by Labex EpiGenMed, an Investissements d’avenir program (ANR-10-LABX-12-01 to N.J.A. and S.N.), the Agence National de la Recherche sur le SIDA et les Hépatites virales, ANRS (AO2017-1 to J.-P.H.), the European Community’s Seventh Framework Program (FP7- PEOPLE-2011-ITN) under the Marie-Curie Initial Training Network FishForPharma (PITN-GA-2011-289209 to G.L.), the European Community’s H2020 Program Marie-Curie Innovative Training Network ImageInLife (721537 to G.L. and J.-P.L.), the Agence Nationale de la Recherche (ANR-16-CE20-0002-03 and ANR-10-MDI-009 to J.-P.L.), and the Région Occitanie (REPERE2017ImageInLife to G.L.). G.M. (AO2018-2), N.S. (AO2016-1), O.M. (AO2017-1), and S.M. (AO2017-2) were supported by grants from the ANRS. This work received help and expertise from TACGene, which is supported by the program Investissement d’avenir TEFOR (ANR-II-INSB-0014). N.S. acknowledges support from the European Molecular Biology Organization EMBO for Fellowship (LT-834-2017), the start-up funding program 'Baustein' of the Medical Faculty of Ulm University (LSBN.0147), and the Deutsche Forschungsgemeinschaft DFG (SM 544/1-1)., ANR-10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010), ANR-16-CE20-0002,Fish-RNAvax,Vaccins ARN éco-compatibles pour l'induction de réponses immunitaires protectrices chez le poisson d'élevage(2016), ANR-10-MIDI-0009,ZebraFlam,Signaux et cellules de la réponse inflammatoire: suivi en temps réel chez un vertébré entier, le danio zébré(2010), ANR-11-INBS-0014,TEFOR,Transgenèse pour les Etudes Fonctionnelles sur les Organismes modèles(2011), European Project: 289209,EC:FP7:PEOPLE,FP7-PEOPLE-2011-ITN,FISHFORPHARMA(2012), European Project: 721537,ImageInLife(2017), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), ANR-10-LABX-0012/10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010), ANR: 11-INBS-0014,TEFOR,Transgenèse pour les Etudes Fonctionnelles sur les Organismes modèles(2011), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Small interfering RNA, Interferon Regulatory Factor-7, Ubiquitin-Protein Ligases, [SDV]Life Sciences [q-bio], Immunology, Regulator, Nerve Tissue Proteins, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Ubiquitin, Interferon, medicine, Animals, Humans, Phosphorylation, RNA, Small Interfering, Research Articles, Zebrafish, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Innate immune system, biology, Influenza A Virus, H3N2 Subtype, SciAdv r-articles, hemic and immune systems, Dendritic Cells, Tripartite motif family, Immunity, Innate, 3. Good health, Cell biology, NIMA-Interacting Peptidylprolyl Isomerase, HEK293 Cells, Interferon Type I, biology.protein, PIN1, HIV-1, IRF7, [SDV.IMM]Life Sciences [q-bio]/Immunology, RNA Interference, Carrier Proteins, Chikungunya virus, 030215 immunology, medicine.drug, Research Article, Signal Transduction
Abstract

TRIM8 and Pin1 oppositely control IRF7-induced interferon production., Plasmacytoid dendritic cells (pDCs) play a crucial role in antiviral innate immunity through their unique capacity to produce large amounts of type I interferons (IFNs) upon viral detection. Tripartite motif (TRIM) proteins have recently come forth as important modulators of innate signaling, but their involvement in pDCs has not been investigated. Here, we performed a rationally streamlined small interfering RNA (siRNA)–based screen of TRIM proteins in human primary pDCs to identify those that are critical for the IFN response. Among candidate hits, TRIM8 emerged as an essential regulator of IFN regulatory factor 7 (IRF7) function. Mechanistically, TRIM8 protects phosphorylated IRF7 (pIRF7) from proteasomal degradation in an E3 ubiquitin ligase–independent manner by preventing its recognition by the peptidyl-prolyl isomerase Pin1. Our findings uncover a previously unknown regulatory mechanism of type I IFN production in pDCs by which TRIM8 and Pin1 oppositely regulate the stability of pIRF7.

Published
2019
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4. Identification of the CCR5-Delta32 HIV resistance allele and new mutations of the CCR5 gene in different Tunisian populations

Author

Karima Fadhlaoui-Zid, Asma Jlizi, Amine Slim, Joanne Edouard, Sabah Frigi, Ioannis Theodorou, Wassila Carpentier, Patrice Debré, and Amel Ben Ammar El Gaaied

Subjects
Adult, Male, Tunisia, Genotype, Receptors, CCR5, Immunology, Population, Single-nucleotide polymorphism, HIV Infections, Biology, medicine.disease_cause, Gene Frequency, medicine, Immunology and Allergy, Humans, Allele, education, Allele frequency, Alleles, Genetics, Mutation, education.field_of_study, Polymorphism, Genetic, Point mutation, Haplotype, General Medicine, Virology, Immunity, Innate, Haplotypes, HIV-1, Female
Abstract

Polymorphisms in some chemokine receptor genes are associated with susceptibility to and progression of human immunodeficiency virus-1 (HIV-1) infection. Most mutations detected in the CC-chemokine receptor 5 (CCR5) gene are specific to different populations. In this study, we focused on polymorphisms of the CCR5 coding region in three healthy populations from Tunisia, corresponding to a cosmopolitan population from Tunis, and two isolated Berber populations. In addition to the CCR5-Delta32 deletion, eleven single nucleotide polymorphisms were detected. Some of these point mutations were associated with the same genotype and even the same haplotype. The (L55Q-C101X), I124, V131F, T143N, A159V, I237, T239A and G301R alleles have not been described previously, whereas the CCR5-Delta32, L55Q, A335V and Y339F variants have already been reported in the literature. The distribution and frequency of these variants were different among the three groups studied, a result in agreement with the mosaic genetic structure of the Tunisian population. To determine whether these alleles affect HIV-1 transmission, we compared allele frequencies between healthy and HIV-1 infected individuals from Tunis. The frequency of the CCR5-Delta32 variant was significantly different between the two groups, leading us to conclude that this mutation might confer protection against HIV infection in Tunisian populations.

Published
2007

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