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19 results on '"Florence Besse"'

1. Tyramine induces dynamic RNP granule remodeling and translation activation in the Drosophila brain

Author

Florence Besse, Nadia Formicola, Anne-Sophie Lancelot, Mounia Lagha, Jeremy Dufourt, Akira Nakamura, Marjorie Heim, 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 Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Kumamoto University, RUIZ, Caroline, Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)

Subjects
ZBP1, QH301-705.5, Science, translation, RNA-binding protein, General Biochemistry, Genetics and Molecular Biology, RNP condensates, 03 medical and health sciences, 0302 clinical medicine, Ca2+/calmodulin-dependent protein kinase, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biology (General), 030304 developmental biology, Ribonucleoprotein, 0303 health sciences, D. melanogaster, General Immunology and Microbiology, biology, Chemistry, General Neuroscience, Helicase, RNA, Translation (biology), Cell Biology, General Medicine, neuron, Cell biology, live-imaging, biology.protein, Medicine, Translational Activation, Drosophila, RNA binding proteins, 030217 neurology & neurosurgery, Research Article
Abstract

Ribonucleoprotein (RNP) granules are dynamic condensates enriched in regulatory RNA binding proteins (RBPs) and RNAs under tight spatiotemporal control. Extensive recent work has investigated the molecular principles underlying RNP granule assembly, unraveling that they form through the self-association of RNP components into dynamic networks of interactions. How endogenous RNP granules respond to external stimuli to regulate RNA fate is still largely unknown. Here, we demonstrate through high-resolution imaging of intact Drosophila brains that Tyramine induces a reversible remodeling of somatic RNP granules characterized by the decondensation of granule-enriched RBPs (e.g. Imp/ZBP1/IGF2BP) and helicases (e.g. Me31B/DDX-6/Rck). Furthermore, our functional analysis reveals that Tyramine signals both through its receptor TyrR and through the calcium-activated kinase CamkII to trigger RNP component decondensation. Finally, we uncover that RNP granule remodeling is accompanied by the rapid and specific translational activation of associated mRNAs. Thus, this work sheds new light on the mechanisms controlling cue-induced rearrangement of physiological RNP condensates.

Published
2021

2. Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in Drosophila neuroblast tumors

Author

Raphaël Clément, Nuno Miguel Luis, Sophie Foppolo, Cédric Maurange, Karine Narbonne-Reveau, Florence Besse, Cassandra Gaultier, Fabrice Daian, Sara Genovese, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), National Institute of Child Health and Human Development [Bethesda], National Institutes of Health, Université Nice Sophia Antipolis (1965 - 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)

Subjects
syncrip, 0301 basic medicine, cancer stem cell, QH301-705.5, Science, [SDV]Life Sciences [q-bio], Cell, Tumor initiation, Biology, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Neural Stem Cells, Neuroblast, Cancer stem cell, medicine, Animals, Humans, Biology (General), Cancer Biology, Body Patterning, Cell Proliferation, Neurons, D. melanogaster, General Immunology and Microbiology, General Neuroscience, Asymmetric Cell Division, Imp, Gene Expression Regulation, Developmental, Cell Differentiation, General Medicine, Pediatric cancer, Neural stem cell, pediatric cancer, Cell biology, Drosophila melanogaster, 030104 developmental biology, medicine.anatomical_structure, Larva, 030220 oncology & carcinogenesis, Medicine, tumor hierarchy, Research Advance, Developmental biology, temporal patterning, Developmental Biology
Abstract

International audience; It is still unclear what drives progression of childhood tumors. During Drosophila larval development, asymmetrically-dividing neural stem cells, called neuroblasts, progress through an intrinsic temporal patterning program that ensures cessation of divisions before adulthood. We previously showed that temporal patterning also delineates an early developmental window during which neuroblasts are susceptible to tumor initiation (Narbonne-Reveau et al., 2016). Using single-cell transcriptomics, clonal analysis and numerical modeling, we now identify a network of twenty larval temporal patterning genes that are redeployed within neuroblast tumors to trigger a robust hierarchical division scheme that perpetuates growth while inducing predictable cell heterogeneity. Along the hierarchy, temporal patterning genes define a differentiation trajectory that regulates glucose metabolism genes to determine the proliferative properties of tumor cells. Thus, partial redeployment of the temporal patterning program encoded in the cell of origin may govern the hierarchy, heterogeneity and growth properties of neural tumors with a developmental origin.

Published
2019

3. Neuronal ribonucleoprotein granules: Dynamic sensors of localized signals

Author

Nadia Formicola, Jeshlee Vijayakumar, and Florence Besse

Subjects
Context (language use), Biology, Cytoplasmic Granules, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Stress, Physiological, Structural Biology, Organelle, Genetics, Protein biosynthesis, Extracellular, Animals, Humans, Molecular Biology, Rapid response, 030304 developmental biology, Ribonucleoprotein, Neurons, 0303 health sciences, Translation (biology), RNP granule, Cell Biology, Cell biology, Ribonucleoproteins, 030217 neurology & neurosurgery, Signal Transduction
Abstract

Membrane-less organelles, because of their capacity to dynamically, selectively and reversibly concentrate molecules, are very well adapted for local information processing and rapid response to environmental fluctuations. These features are particularly important in the context of neuronal cells, where synapse-specific activation, or localized extracellular cues, induce signaling events restricted to specialized axonal or dendritic subcompartments. Neuronal ribonucleoprotein (RNP) particles, or granules, are nonmembrane bound macromolecular condensates that concentrate specific sets of mRNAs and regulatory proteins, promoting their long-distance transport to axons or dendrites. Neuronal RNP granules also have a dual function in regulating the translation of associated mRNAs: while preventing mRNA translation at rest, they fuel local protein synthesis upon activation. As revealed by recent work, rapid and reversible switches between these two functional modes are triggered by modifications of the networks of interactions underlying RNP granule assembly. Such flexible properties also come with a cost, as neuronal RNP granules are prone to transition into pathological aggregates in response to mutations, aging, or cellular stresses, further emphasizing the need to better understand the mechanistic principles governing their dynamic assembly and regulation in living systems.

Published
2019

4. Detecting and quantifying stress granules in tissues of multicellular organisms with the Obj.MPP analysis tool

Author

Eric Debreuve, Arnaud Hubstenberger, Alia Bahri, Xavier Descombes, Fabienne De Graeve, Somia Rahmoun, Szilvia Ecsedi, Florence Besse, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Morphologie et Images (MORPHEME), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut de Biologie Valrose (IBV), 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)-Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), 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), 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)-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)-Signal, Images et Systèmes (Laboratoire I3S - SIS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS)

Subjects
stress granules, Context (language use), Cytoplasmic Granules, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Stress granule, Limit of Detection, Stress, Physiological, Structural Biology, image analysis, Image Processing, Computer-Assisted, Genetics, Animals, marked point process, Caenorhabditis elegans, Molecular Biology, Gene, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030304 developmental biology, Ribonucleoprotein, Motor Neurons, 0303 health sciences, biology, Optical Imaging, detection algorithm, Cell Biology, biology.organism_classification, Cell biology, Multicellular organism, Drosophila melanogaster, Ribonucleoproteins, Signal transduction, Software, 030217 neurology & neurosurgery, Genetic screen
Abstract

International audience; Stress Granules (SGs) are macromolecular assemblies induced by stress and composed of proteins and mRNAs stalled in translation initiation. SGs play an important role in the response to stress and in the modulation of signaling pathways. Furthermore, these structures are related to the pathological ribonucleoprotein (RNP) aggregates found in neurodegenerative disease contexts, highlighting the need to understand how they are formed and recycled in normal and pathological contexts. Although genetically tractable multicellular organisms have been key in identifying modifiers of RNP aggregate toxicity, in vivo analysis of SG properties and regulation has lagged behind, largely due to the difficulty of detecting SG from images of intact tissues. Here, we describe the object detector software Obj.MPP and show how it overcomes the limits of classical object analyzers to extract the properties of SGs from wide-field and confocal images of respectively C. elegans and Drosophila tissues. We demonstrate that Obj.MPP enables the identification of genes modulating the assembly of endogenous and pathological SGs, and thus that it will be useful in the context of future genetic screens and in vivo studies. This article is protected by copyright. All rights reserved.

Published
2019

5. Local Translation in Axons: When Membraneless RNP Granules Meet Membrane-Bound Organelles

Author

Florence Besse, Kavya Vinayan Pushpalatha, Besse, Florence, 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), Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and RUIZ, Caroline

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], RNA transport, Review, Mitochondrion, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, 03 medical and health sciences, 0302 clinical medicine, local translation, Gene expression, Organelle, medicine, Protein biosynthesis, Molecular Biosciences, Axon, Molecular Biology, lcsh:QH301-705.5, Ribonucleoprotein, axon, Messenger RNA, RNP granules, Chemistry, Cell biology, mitochondria, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), 030220 oncology & carcinogenesis, vesicular trafficking
Abstract

International audience; Eukaryotic cell compartmentalization relies on long-known membrane-delimited organelles, as well as on more recently discovered membraneless macromolecular condensates. How these two types of organelles interact to regulate cellular functions is still largely unclear. In this review, we highlight how membraneless ribonucleoprotein (RNP) organelles, enriched in RNAs and associated regulatory proteins, cooperate with membrane-bound organelles for tight spatio-temporal control of gene expression in the axons of neuronal cells. Specifically, we present recent evidence that motile membrane-bound organelles are used as vehicles by RNP cargoes, promoting the long-range transport of mRNA molecules to distal axons. As demonstrated by recent work, membrane-bound organelles also promote local protein synthesis, by serving as platforms for the local translation of mRNAs recruited to their outer surface. Furthermore, dynamic and specific association between RNP cargoes and membrane-bound organelles is mediated by bi-partite adapter molecules that interact with both types of organelles selectively, in a regulated-manner. Maintaining such a dynamic interplay is critical, as alterations in this process are linked to neurodegenerative diseases. Together, emerging studies thus point to the coordination of membrane-bound and membraneless organelles as an organizing principle underlying local cellular responses.

Published
2019

6. Cooption of antagonistic RNA-binding proteins establishes cell hierarchy in Drosophila neuro-developmental tumors

Author

Nuno Miguel Luis, Sophie Foppolo, Cédric Maurange, Fabrice Daian, Cassandra Gaultier, Karine Narbonne-Reveau, Raphaël Clément, Florence Besse, and Sara Genovese

Subjects
0303 health sciences, Transition (genetics), Cancer, RNA-binding protein, Biology, medicine.disease, Tumor heterogeneity, 3. Good health, Cell biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, Tumor growth, Progenitor cell, Developmental biology, 030304 developmental biology
Abstract

The mechanisms that govern the hierarchical organization of tumors are still poorly understood, especially in highly heterogeneous neural cancers. Previously, we had shown that aggressive neural tumors can be induced upon dedifferentiation of susceptible intermediate progenitors produced during early development (Narbonne-Reveau et al., 2016). Using clonal analysis, stochastic modelling and single-cell transcriptomics, we now find that such tumors rapidly become heterogeneous, containing progenitors with different proliferative potentials. We demonstrate that tumor heterogeneity emerges from the deregulated transition between two antagonistic RNA-binding proteins, Imp and Syncrip, that switch neural progenitors from a default self-renewing to a differentiation-prone state during development. Consequently, aberrant maintenance of Imp confers a cancer stem cell-like identity as Imp+ progenitors sustain tumor growth while being able to continuously generate Syncrip+ progenitors. The latter exhibit limited self-renewal likely due to Syncrip-mediated metabolic exhaustion. This study provides an example of how a subverted developmental transition establishes a hierarchical tumor.

Published
2018
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7. A Stochastic Framework for Neuronal Morphological Comparison: Application to the Study of imp Knockdown Effects in Drosophila Gamma Neurons

Author

Xavier Descombes, Florence Besse, Caroline Medioni, Agustina Razetti, Morphologie et Images (MORPHEME), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-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)-Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Biologie Valrose (IBV), 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), Ana Fred, Hugo Gamboa, Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Signal, Images et Systèmes (Laboratoire I3S - SIS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and Razetti, Agustina

Subjects
0301 basic medicine, Regulator, Biology, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Gamma neurons, medicine, Axon, Maximum likelihood analysis, Actin, Gene knockdown, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Wild type, Remodelling, Phenotype, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cell biology, Stochastic models, 030104 developmental biology, medicine.anatomical_structure, Profilin, nervous system, biology.protein, Neuron, 030217 neurology & neurosurgery
Abstract

9th International Joint Conference, BIOSTEC 2016, Rome, Italy, February 21–23, 2016, Revised Selected Papers; International audience; In order to reach their final adult morphology, Gamma neurons in Drosophila brain undergo a process of pruning followed by regrowth of their main axons and branches called remodelling. The mRNA binding protein Imp was identified to play a fundamental role in this process. One of Imp targets, profilin mRNA, encodes for an actin regulator that has been shown to be involved in axon remodelling. In this paper we intend to further understand the role of Imp and the importance of profilin mRNA expression regulation during remodelling. To do so, we propose a stochastic framework to exhaustively compare the adult morphology between wild type (WT), imp knockdown (Imp) and imp knockdown rescued by Profilin (Prof Rescue) neurons. Our framework consists in (i) the selection of the main neuron morphological features, (ii) their stochastic modelling and parameter estimation from data and (iii) a maximum likelihood analysis for each individual neuron to quantitatively assess the similarity or difference between groups. Thanks to this framework we show that imp mutant neurons can be divided in two phenotypical groups with a different aberrancy degree, and that profilin overexpression partially rescues the main axon and branch development thereby it reduces the proportion of neurons with the strongest remodelling phenotype.

Published
2017

8. Linking amyotrophic lateral sclerosis and spinal muscular atrophy through RNA-transcriptome homeostasis: a genomics perspective

Author

Florence Besse, Javier De Las Rivas, Margarida Gama-Carvalho, Francisco R. Pinto, Marina L. Garcia-Vaquero, Jörg B. Schulz, Joachim Weis, Aaron Voigt, European Commission, Agence Nationale de la Recherche (France), Fundação para a Ciência e a Tecnologia (Portugal), Instituto de Salud Carlos III, and Federal Ministry of Education and Research (Germany)

Subjects
0301 basic medicine, RNA polymerase II, Biology, Biochemistry, Muscular Atrophy, Spinal, Transcriptome, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Transcription (biology), Databases, Genetic, medicine, Animals, Homeostasis, Humans, Transcriptome homeostasis, SMA, Amyotrophic lateral sclerosis, Transcriptomics, RNA metabolism, Amyotrophic Lateral Sclerosis, Neurodegeneration, RNA, Genomics, Spinal muscular atrophy, medicine.disease, Chromatin, 030104 developmental biology, biology.protein, ALS, Neuroscience, 030217 neurology & neurosurgery
Abstract

In this review, we present our most recent understanding of key biomolecular processes that underlie two motor neuron degenerative disorders, amyotrophic lateral sclerosis, and spinal muscular atrophy. We focus on the role of four multifunctional proteins involved in RNA metabolism (TDP-43, FUS, SMN, and Senataxin) that play a causal role in these diseases. Recent results have led to a novel scenario of intricate connections between these four proteins, bringing transcriptome homeostasis into the spotlight as a common theme in motor neuron degeneration. We review reported functional and physical interactions between these four proteins, highlighting their common association with nuclear bodies and small nuclear ribonucleoprotein particle biogenesis and function. We discuss how these interactions are turning out to be particularly relevant for the control of transcription and chromatin homeostasis, including the recent identification of an association between SMN and Senataxin required to ensure the resolution of DNA-RNA hybrid formation and proper termination by RNA polymerase II. These connections strongly support the existence of common pathways underlying the spinal muscular atrophy and amyotrophic lateral sclerosis phenotype. We also discuss the potential of genome-wide expression profiling, in particular RNA sequencing derived data, to contribute to unravelling the underlying mechanisms. We provide a review of publicly available datasets that have addressed both diseases using these approaches, and highlight the value of investing in cross-disease studies to promote our understanding of the pathways leading to neurodegeneration., This work is part of an EU Joint Programme – Neurodegenerative Disease Research (JPND) project with the acronym ‘Fly-SMALS’. The project is supported through the following funding organisations under the aegis of JPND – www.jpnd.eu: France, Agence Nationale de la Recherche; Germany, Bundesministerium für Bildung und Forschung (BMBF); Portugal, Fundaçao para a Ciência e a Tecnologia and Spain, Instituto de Salud Carlos III (ISCIII). Associated to the JPND, the group of JDLR was funded for this work by the ISCIII and FEDER through projects AC14/00024 and PI15/00328. Work in MGC’s group was supported by the grant JPND-CD/0002/2013 and FCT/MCTES/PIDDAC research center grant to BioISI UID/MULTI/04046/2013. Work in F.B.’s group is supported by the ANR (through the RNAGRIMP research grant and the ‘Investments for the Future’ LABEX SIGNALIFE program # ANR-11-LABX-0028-01). Work on ALS in Joachim Weis’s group was supported by funding from BMBF, IZKF Aachen (N7–4), the Deutsche Gesellschaft für Muskelkranke (DGM) and the Initiative Therapieforschung ALS.

Published
2017

9. Imp Promotes Axonal Remodeling by Regulating profilin mRNA during Brain Development

Author

Caroline Medioni, Anne Ephrussi, Mirana Ramialison, Florence Besse, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 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), Université Nice Sophia Antipolis (1965 - 2019) (UNS), European Molecular Biology Laboratory [Heidelberg] (EMBL), and MEDIONI, Caroline

Subjects
[SDV]Life Sciences [q-bio], Ramification (botany), Regulator, RNA-binding protein, General Biochemistry, Genetics and Molecular Biology, Profilins, 03 medical and health sciences, 0302 clinical medicine, Neurites, medicine, Animals, Drosophila Proteins, MRNA transport, RNA, Messenger, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Mushroom Bodies, 030304 developmental biology, Neurons, 0303 health sciences, Messenger RNA, biology, Agricultural and Biological Sciences(all), Biochemistry, Genetics and Molecular Biology(all), fungi, Brain, RNA-Binding Proteins, Anatomy, Axons, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Profilin, nervous system, Larva, Mushroom bodies, biology.protein, Drosophila, Neuron, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery
Abstract

International audience; : Neuronal remodeling is essential for the refinement of neuronal circuits in response to developmental cues [1-4]. Although this process involves pruning or retraction of axonal projections followed by axonal regrowth and branching, how these steps are controlled is poorly understood. Drosophila mushroom body (MB) γ neurons provide a paradigm for the study of neuronal remodeling, as their larval axonal branches are pruned during metamorphosis and re-extend to form adult-specific branches [5]. Here, we identify the RNA binding protein Imp as a key regulator of axonal remodeling. Imp is the sole fly member of a conserved family of proteins that bind target mRNAs to promote their subcellular targeting [6-12]. We show that whereas Imp is dispensable for the initial growth of MB γ neuron axons, it is required for the regrowth and ramification of axonal branches that have undergone pruning. Furthermore, Imp is actively transported to axons undergoing developmental remodeling. Finally, we demonstrate that profilin mRNA is a direct and functional target of Imp that localizes to axons and controls axonal regrowth. Our study reveals that mRNA localization machineries are actively recruited to axons upon remodeling and suggests a role of mRNA transport in developmentally programmed rewiring of neuronal circuits during brain maturation.

Published
2014
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10. From Curves to Trees: A Tree-like Shapes Distance Using the Elastic Shape Analysis Framework

Author

Alejandro Mottini, Florence Besse, Xavier Descombes, Morphologie et Images (MORPHEME), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-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)-Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (IBV), 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), Université Nice Sophia Antipolis (... - 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)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS)

Subjects
[SDV]Life Sciences [q-bio], Models, Neurological, Population, Classification scheme, axons, tree metrics, Pattern Recognition, Automated, Trees, 03 medical and health sciences, [SPI]Engineering Sciences [physics], Imaging, Three-Dimensional, 0302 clinical medicine, Medical imaging, Humans, Computer vision, education, 030304 developmental biology, Mathematics, Neurons, 0303 health sciences, education.field_of_study, business.industry, General Neuroscience, Decision Trees, Pattern recognition, Lung airways, classification, Artificial intelligence, elastic shape metrics, business, 030217 neurology & neurosurgery, Software, Information Systems, Shape analysis (digital geometry)
Abstract

International audience; Trees are a special type of graph that can be found in various disciplines. In the field of biomedical imaging, trees have been widely studied as they can be used to describe structures such as neurons, blood vessels and lung airways. It has been shown that the morphological characteristics of these structures can provide information on their function aiding the characterization of pathological states. Therefore, it is important to develop methods that analyze their shape and quantify differences between their structures. In this paper, we present a method for the comparison of tree-like shapes that takes into account both topological and geometrical information. This method, which is based on the Elastic Shape Analysis Framework, also computes the mean shape of a population of trees. As a first application, we have considered the comparison of axon morphology. The performance of our method has been evaluated on two sets of images. For the first set of images, we considered four different populations of neurons from different animals and brain sections from the NeuroMorpho.org open database. The second set was composed of a database of 3D confocal microscopy images of three populations of axonal trees (normal and two types of mutations) of the same type of neurons. We have calculated the inter and intra class distances between the populations and embedded the distance in a classification scheme. We have compared the performance of our method against three other state of the art algorithms, and results showed that the proposed method better distinguishes between the populations. Furthermore, we present the mean shape of each population. These shapes present a more complete picture of the morphological characteristics of each population, compared to the average value of certain predefined features.

Published
2015

11. The TRIM-NHL protein Brat promotes axon maintenance by repressing src64B expression

Author

Ilka Reichardt, Giovanni Marchetti, Florence Besse, Juergen A. Knoblich, Institut de Biologie Valrose (IBV), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)

Subjects
Transcription, Genetic, Regulator, Biology, 03 medical and health sciences, 0302 clinical medicine, Proto-Oncogene Proteins, Neural Pathways, medicine, Animals, Drosophila Proteins, Axon, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030304 developmental biology, 0303 health sciences, General Neuroscience, Translation (biology), Articles, Protein-Tyrosine Kinases, Phenotype, Axons, DNA-Binding Proteins, Drosophila melanogaster, src-Family Kinases, medicine.anatomical_structure, nervous system, Mushroom bodies, Signal transduction, Neuroscience, 030217 neurology & neurosurgery, Function (biology)
Abstract

The morphology and the connectivity of neuronal structures formed during early development must be actively maintained as the brain matures. Although impaired axon stability is associated with the progression of various neurological diseases, relatively little is known about the factors controlling this process. We identified Brain tumor (Brat), a conserved member of the TRIM-NHL family of proteins, as a new regulator of axon maintenance inDrosophilaCNS. Brat function is dispensable for the initial growth of Mushroom Body axons, but is required for the stabilization of axon bundles. We found that Brat represses the translation ofsrc64B, an upstream regulator of a conserved Rho-dependent pathway previously shown to promote axon retraction. Furthermore,bratphenotypes are phenocopied bysrc64Boverexpression, and partially suppressed by reducing the levels ofsrc64Bor components of the Rho pathway, suggesting thatbratpromotes axon maintenance by downregulating the levels of Src64B. Finally, Brat regulates brain connectivity via its NHL domain, but independently of its previously described partners Nanos, Pumilio, and d4EHP. Thus, our results uncover a novel post-transcriptional regulatory mechanism that controls the maintenance of neuronal architecture by tuning the levels of a conserved rho-dependent signaling pathway.

Published
2014

12. Discrete stochastic model for the generation of axonal trees

Author

Florence Besse, Eugene Pechersky, Alejandro Mottini, Xavier Descombes, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 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), Morphologie et Images (MORPHEME), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut de Biologie Valrose (IBV), 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)-Université Nice Sophia Antipolis (... - 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)-Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Dobrushin laboratory of Mathematics (IITP), Institute for Information Transmission Problems, 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)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS)

Subjects
Neurite, Stochastic modelling, Green Fluorescent Proteins, Models, Neurological, Mutant, law.invention, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Confocal microscopy, law, Animals, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, Probability, 030304 developmental biology, Stochastic Processes, 0303 health sciences, biology, Markov chain, Stochastic process, biology.organism_classification, Axons, Markov Chains, Drosophila melanogaster, Mutation, Biological system, Neuroscience, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, 030217 neurology & neurosurgery, Biogenesis
Abstract

International audience; In this work we propose a 2D discrete stochastic model for the simulation of axonal biogenesis. The model is defined by a third order Markov Chain. The model considers two main processes: the growth process that models the elongation and shape of the neurites and the bifurcation process that models the generation of branches. The growth process depends, among other variables, on the external attraction field generated by a chemoattractant molecule secreted by the target area. We propose an estimation scheme of the involved parameters from real fluorescent confocal microscopy images of single neurons within intact adult Drosophila fly brains. Both normal neurons and neurons in which certain genes were inactivated have been considered (two mutations). In total, 53 images (18 normal, 21 type 1 mutant and 14 type 2 mutant) were used. The model parameters allow us to describe pathological characteristics of the mutated populations.

Published
2014

13. Axonal Tree Classification Using an Elastic Shape Analysis Based Distance

Author

Florence Besse, Xavier Descombes, Alejandro Mottini, Morphologie et Images (MORPHEME), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-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)-Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (IBV), 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), Université Nice Sophia Antipolis (... - 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)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS)

Subjects
business.industry, 02 engineering and technology, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, 0202 electrical engineering, electronic engineering, information engineering, 020201 artificial intelligence & image processing, Computer vision, Artificial intelligence, business, Algorithm, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, Mathematics, Shape analysis (digital geometry)
Abstract

International audience

Published
2014

14. Principles and roles of mRNA localization in animal development

Author

Florence Besse, Kimberly L. Mowry, Caroline Medioni, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 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), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Brown University, and MEDIONI, Caroline

Subjects
Cytoplasm, RNA localization, [SDV]Life Sciences [q-bio], MESH: Asymmetric Cell Division, Reviews, Biology, 03 medical and health sciences, 0302 clinical medicine, Cell polarity, Asymmetric cell division, Animals, MESH: Animals, RNA, Messenger, Molecular Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030304 developmental biology, Body Patterning, MESH: RNA, Messenger, 0303 health sciences, Mechanism (biology), MESH: Cytoplasm, Asymmetric Cell Division, Cell Polarity, Cell migration, Embryonic stem cell, Cell biology, [SDV] Life Sciences [q-bio], MESH: Cell Polarity, 030217 neurology & neurosurgery, Intracellular, Developmental Biology, MESH: Body Patterning
Abstract

International audience; Intracellular targeting of mRNAs has long been recognized as a means to produce proteins locally, but has only recently emerged as a prevalent mechanism used by a wide variety of polarized cell types. Localization of mRNA molecules within the cytoplasm provides a basis for cell polarization, thus underlying developmental processes such as asymmetric cell division, cell migration, neuronal maturation and embryonic patterning. In this review, we describe and discuss recent advances in our understanding of both the regulation and functions of RNA localization during animal development.

Published
2012

15. Axon extraction from fluorescent confocal microscopy images

Author

Alejandro Mottini, Florence Besse, Xavier Descombes, Morphologie et Images (MORPHEME), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-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)-Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institute of Developmental Biology and Cancer (IBDC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), IEEE Signal Processing Society (SPS) and IEEE Engineering in Medicine and Biology Society (EMBS), Université Nice Sophia Antipolis (... - 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)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS)

Subjects
Computer science, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, Skeletonization, 030218 nuclear medicine & medical imaging, law.invention, 03 medical and health sciences, 0302 clinical medicine, Optical microscope, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, law, Confocal microscopy, Microscopy, medicine, Computer vision, axon extraction, Axon, 030304 developmental biology, 0303 health sciences, business.industry, Extraction (chemistry), Image segmentation, Real image, Fluorescence, medicine.anatomical_structure, nervous system, Gabor functions, fluorescent confocal microscopy, Artificial intelligence, tensor voting, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract

International audience; The morphological analysis of axonal trees is an important problem in neuroscience. The first step for such an analysis is the extraction of the axon. Due to the high volume of generated image data and the tortuous nature of the axons, manual processing is not feasible. Therefore, it is necessary to develop techniques for the automatic extraction of the neuronal structures. In this paper we present a new approach for the automatic extraction of axons from fluorescent confocal microscopy images. It combines algorithms for filament enhancement, binarization, skeletonization and gap filling in a pipeline capable of extracting the axons. The performance of the proposed method was evaluated on real images. Results support the potential use of this technique in helping biologists perform automatic extraction of axons from fluorescent confocal microscopy images.

Published
2012

16. Age differences in outdated information processing during news reports reading

Author

Florence Besse, Pascale Maury, Sophie Martin, Institute of Developmental Biology and Cancer (IBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'ingénierie pour les systèmes complexes (UR LISC), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)

Subjects
Male, Aging, Inference, MESH: Mental Recall, MESH: Comprehension, MESH: Semantics, Developmental psychology, Cohort Studies, 0302 clinical medicine, Mental Processes, Reading (process), Task Performance and Analysis, Attention, Young adult, MESH: Cohort Studies, [SDV.BDD]Life Sciences [q-bio]/Development Biology, General Psychology, MESH: Mental Processes, media_common, MESH: Aged, 05 social sciences, MESH: Research Design, Information processing, Age Factors, Cognition, Causality, Semantics, MESH: Young Adult, Research Design, Female, Psychology, Comprehension, media_common.quotation_subject, MESH: Reading, 050105 experimental psychology, 03 medical and health sciences, Young Adult, Arts and Humanities (miscellaneous), Humans, 0501 psychology and cognitive sciences, Aged, MESH: Age Factors, MESH: Attention, MESH: Humans, Age differences, MESH: Task Performance and Analysis, MESH: Male, MESH: Medical Informatics, Reading, Mental Recall, Geriatrics and Gerontology, MESH: Female, 030217 neurology & neurosurgery, Medical Informatics
Abstract

International audience; In two experiments, the authors explored whether there are any age differences associated with the ability to process outdated information during news reports comprehension. Younger and older participants (mean age: 70 years old) read passages in which a cause was first said to be responsible for the occurrence of a news event. New elements emerged from the investigation in progress and revealed that the original cause was incorrect. Inference response times indicated that older adults more than younger ones took advantage of an alternative cause mentioned in the text to put the outdated information in the background, whereas younger readers probably kept both causes activated. The research tested the concepts involved with age differences in updating situation model.

Published
2010

17. Drosophila PTB promotes formation of high-order RNP particles and represses oskar translation

Author

Virginie Marchand, Florence Besse, Sonia López de Quinto, Alvar Trucco, Anne Ephrussi, Institut de signalisation, biologie du développement et cancer (ISBDC), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Lillois d’Études et de Recherches Sociologiques et Économiques - UMR 8019 (CLERSÉ), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), and Centre National de la Recherche Scientifique (CNRS)-Université de Lille

Subjects
oskar, environment and public health, Oogenesis, 0302 clinical medicine, MESH: Gene Expression Regulation, Developmental, Protein biosynthesis, Drosophila Proteins, MESH: Animals, 3' Untranslated Regions, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Ribonucleoprotein, 0303 health sciences, biology, Gene Expression Regulation, Developmental, Translation (biology), MESH: 3' Untranslated Regions, MESH: Oogenesis, Cell biology, Drosophila melanogaster, Ribonucleoproteins, MESH: Protein Biosynthesis, Translational Activation, Female, MESH: Polypyrimidine Tract-Binding Protein, Polypyrimidine Tract-Binding Protein, Protein Binding, MESH: Mutation, MESH: Drosophila Proteins, MESH: Drosophila melanogaster, 03 medical and health sciences, MESH: Gene Expression Profiling, Genetics, Animals, MRNA transport, MESH: Protein Binding, Polypyrimidine tract-binding protein, 030304 developmental biology, Binding Sites, Three prime untranslated region, urogenital system, Gene Expression Profiling, Molecular biology, MESH: Ribonucleoproteins, MESH: Binding Sites, Protein Biosynthesis, Mutation, biology.protein, MESH: Female, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Local translation of asymmetrically enriched mRNAs is a powerful mechanism for functional polarization of the cell. In Drosophila, exclusive accumulation of Oskar protein at the posterior pole of the oocyte is essential for development of the future embryo. This is achieved by the formation of a dynamic oskar ribonucleoprotein (RNP) complex regulating the transport of oskar mRNA, its translational repression while unlocalized, and its translational activation upon arrival at the posterior pole. We identified the nucleo–cytoplasmic shuttling protein PTB (polypyrimidine tract-binding protein)/hnRNP I as a new factor associating with the oskar RNP in vivo. While PTB function is largely dispensable for oskar mRNA transport, it is necessary for translational repression of the localizing mRNA. Unexpectedly, a cytoplasmic form of PTB can associate with oskar mRNA and repress its translation, suggesting that nuclear recruitment of PTB to oskar complexes is not required for its regulatory function. Furthermore, PTB binds directly to multiple sites along the oskar 3′ untranslated region and mediates assembly of high-order complexes containing multiple oskar RNA molecules in vivo. Thus, PTB is a key structural component of oskar RNP complexes that dually controls formation of high-order RNP particles and translational silencing.

Published
2009

18. Characterization of the Drosophila myeloid leukemia factor

Author

Anne Plessis, Florence Besse, Séverine Martin-Lannerée, Matthieu Sanial, Christelle Lasbleiz, Hervé Tricoire, Sylvaine Fouix, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Laboratoire de génétique et biologie cellulaire (LGBC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and the CNRS, the Universities Paris 6 and 7, the ARC (grant N_4797) and an ACI 'Biologie du developpement et physiologie integrative' (N_525044). The imaging facilities were partially funded by the ARC, the region Ile de France (SESAME) the University Paris 7. the M.R.T. and the 'Ligue contre le cancer.'

Subjects
Cytoplasm, MESH: Sequence Analysis, DNA, Embryo, Nonmammalian, MESH: Sequence Homology, Amino Acid, MESH: Drosophila, MESH: Amino Acid Sequence, MESH: Protein Isoforms, Eye, law.invention, Animals, Genetically Modified, 0302 clinical medicine, law, MESH: Gene Expression Regulation, Developmental, Drosophila Proteins, Protein Isoforms, MESH: Animals, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Conserved Sequence, Genetics, 0303 health sciences, MESH: Conserved Sequence, MESH: Alternative Splicing, Neurodegeneration, Gene Expression Regulation, Developmental, Myeloid leukemia, MESH: Transcription Factors, Immunohistochemistry, Phenotype, Hedgehog signaling pathway, 3. Good health, MESH: Repressor Proteins, Drosophila, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Subcellular Fractions, Premature aging, MESH: Cell Nucleus, MESH: Mutation, MESH: Drosophila Proteins, Molecular Sequence Data, MESH: Eye, Biology, MESH: Animals, Genetically Modified, 03 medical and health sciences, medicine, Animals, Amino Acid Sequence, 030304 developmental biology, Cell Nucleus, MESH: Molecular Sequence Data, Sequence Homology, Amino Acid, MESH: Cytoplasm, fungi, MESH: Embryo, Nonmammalian, MESH: Immunohistochemistry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Sequence Analysis, DNA, Cell Biology, medicine.disease, Subcellular localization, Repressor Proteins, Alternative Splicing, MESH: Subcellular Fractions, Mutation, Suppressor, Myeloid leukemia factor 1, 030217 neurology & neurosurgery, Transcription Factors
Abstract

International audience; In human, the myeloid leukemia factor 1 (hMLF1) has been shown to be involved in acute leukemia, and mlf related genes are present in many animals. Despite their extensive representation and their good conservation, very little is understood about their function. In Drosophila, dMLF physically interacts with both the transcription regulatory factor DREF and an antagonist of the Hedgehog pathway, Suppressor of Fused, whose over-expression in the fly suppresses the toxicity induced by polyglutamine. No connection between these data has, however, been established. Here, we show that dmlf is widely and dynamically expressed during fly development. We isolated and analyzed the first dmlf mutants: embryos lacking maternal dmlf product have a low viability with no specific defect, and dmlf(-)- adults display weak phenotypes. We monitored dMLF subcellular localization in the fly and cultured cells. We were able to show that, although generally nuclear, dMLF can also be cytoplasmic, depending on the developmental context. Furthermore, two differently spliced variants of dMLF display differential subcellular localization, allowing the identification of regions of dMLF potentially important for its localization. Finally, we demonstrate that dMLF can act developmentally and postdevelopmentally to suppress neurodegeneration and premature aging in a cerebellar ataxia model.

Published
2006

19. fused regulates germline cyst mitosis and differentiation during Drosophila oogenesis

Author

Claudie Lamour-Isnard, Denise Busson, Florence Besse, Karine Narbonne-Reveau, Anne-Marie Pret, National Institute of Child Health and Human Development [Bethesda], National Institutes of Health, EMBL Heidelberg, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Association pour la Recherche contre le Cancer (ARC) n° 7511 & 4501

Subjects
Germline stem cell, Embryology, Somatic cell, Dpp/TGFβ, Mitosis, Protein Serine-Threonine Kinases, Biology, Nurse cell, Germline, Animals, Genetically Modified, Cell cycle arrest, 03 medical and health sciences, 0302 clinical medicine, Oogenesis, Ovarian Follicle, Ovarian tumor mutants, Animals, Drosophila Proteins, bag of marbles, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030304 developmental biology, Ovarian Neoplasms, Genetics, 0303 health sciences, Cystoblast, [SDV.GEN]Life Sciences [q-bio]/Genetics, Stem Cells, Gene Expression Regulation, Developmental, Drosophila embryogenesis, Cell Differentiation, Immunohistochemistry, Hedgehog signaling pathway, Cell biology, Germ Cells, Drosophila melanogaster, Oocytes, fused, Female, Germline cyst, Oocyte differentiation, Stem cell, 030217 neurology & neurosurgery, Signal Transduction, Developmental Biology
Abstract

The fused gene encodes a serine-threonine kinase that functions as a positive regulator of Hedgehog signal transduction in Drosophila embryogenesis, wing morphogenesis, and somatic cell development during oogenesis. Here, we have characterized the germline ovarian tumors present in adult ovaries of fused mutant females, a phenotype not observed upon deregulation of any other component of Hedgehog signaling. In the strongest fused mutant contexts, we found that tumorous ovarian follicles accumulate early spectrosome-containing germ cells corresponding to germline stem cells and/or early cystoblasts as evidenced by activated Dpp signal transduction and transcriptional repression of bag-of-marbles, encoding the cystoblast determination factor. These early germ cells are maintained far from their usual position in a specialized niche of somatic cells in the apical part of the germarium, which appears normal in size in fused mutant ovarioles. Therefore, these results indicate a novel function for fused in downregulation of Dpp signaling which is necessary for de-repression of bag-of-marbles and consequent cystoblast determination. The abnormal accumulation of these early germ cells seems to be due primarily to defects in differentiation since we show that germline stem cell proliferation in the germarium is not affected. A later block in germline development, at the 16-cell cyst stage before significant nurse cell and oocyte differentiation, was also observed in tumorous follicles when fused function was only partially lowered. Finally, fused mutant ovaries exhibit some germline cysts having undergone a supernumerary fifth mitotic division. Through clonal analysis, we provide evidence that fused regulates these cystocyte divisions cell autonomously, while the tumorous phenotype probably reflects both a somatic and germline requirement for fused for cyst and follicle development.

Published
2006

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