ENS - Départment de biologie

Plasticity of Animal Genome Architecture Unmasked by Rapid Evolution of a Pelagic Tunicate

Marie Embs — 2015-02-25T10:14:43Z

Genomes of animals as different as sponges and humans show conservation of global architecture. Here we show that multiple genomic features including transposon diversity, developmental gene repertoire, physical gene order, and intron-exon organization are shattered in the tunicate Oikopleura, belonging to the sister group of vertebrates and retaining chordate morphology. Ancestral architecture of animal genomes can be deeply modified and may therefore be largely nonadaptive. This rapidly evolving animal lineage thus offers unique perspectives on the level of genome plasticity. It also illuminates issues as fundamental as the mechanisms of intron gain.

Science. 2010 Dec 3 ;330(6009):1381-5.

A crosstalk between β1 and β3 integrins controls glycine receptor and gephyrin trafficking at synapses

Marie Embs — 2015-02-25T09:33:15Z

The regulation of glycine receptor (GlyR) number at synapses is necessary for the efficacy of inhibition and the control of neuronal excitability in the spinal cord. GlyR accumulation at synapses depends on the scaffolding molecule gephyrin and is linked to GlyR synaptic dwell time. However, the mechanisms that tune GlyR synaptic exchanges in response to different neuronal environments are unknown. Integrins are cell adhesion molecules and signaling receptors. Using single quantum dot imaging and fluorescence recovery after photobleaching, we found in rats that β1 and β3 integrins adjust synaptic strength by regulating the synaptic dwell time of both GlyRs and gephyrin. β1 and β3 integrins crosstalked via calcium/calmodulin-dependent protein kinase II and adapted GlyR lateral diffusion and gephyrin-dependent trapping at synapses. This provides a mechanism for maintaining or adjusting the steady state of postsynaptic molecule exchanges and the level of glycinergic inhibition in response to neuron- and glia-derived signals or extracellular matrix remodeling.

Nat Neurosci. 2010 Nov ;13(11):1388-95.

The exon junction complex differentially marks spliced junctions

Marie Embs — 2015-02-25T09:29:32Z

The exon junction complex (EJC), which is deposited onto mRNAs as a consequence of splicing, is involved in multiple post-transcriptional events in metazoa. Here, using Drosophila melanogaster cells, we show that only some introns trigger EJC-dependent nonsense-mediated mRNA decay and that EJC association with particular spliced junctions depends on RNA cis-acting sequences. This study provides the first evidence to our knowledge that EJC deposition is not constitutive but instead is a regulated process.

Nat Struct Mol Biol. 2010 Oct ;17(10):1269-71.

A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression

Marie Embs — 2015-02-25T09:28:08Z

A growing number of long nuclear-retained non-coding RNAs (ncRNAs) have recently been described. However, few functions have been elucidated for these ncRNAs. Here, we have characterized the function of one such ncRNA, identified as metastasis-associated lung adenocar- cinoma transcript 1 (Malat1). Malat1 RNA is expressed in numerous tissues and is highly abundant in neurons. It is enriched in nuclear speckles only when RNA polymerase II-dependent transcription is active. Knock-down studies revealed that Malat1 modulates the recruitment of SR family pre-mRNA-splicing factors to the transcription site of a transgene array. DNA microarray analysis in Malat1- depleted neuroblastoma cells indicates that Malat1 con- trols the expression of genes involved not only in nuclear processes, but also in synapse function. In cultured hippo- campal neurons, knock-down of Malat1 decreases synap- tic density, whereas its over-expression results in a cell- autonomous increase in synaptic density. Our results suggest that Malat1 regulates synapse formation by mod- ulating the expression of genes involved in synapse for- mation and/or maintenance.

EMBO J. 2010 Sep 15 ;29(18):3082-93.

Chris Bowler Silver medal of CNRS

Marie Embs — 2015-02-25T09:22:31Z

His favourite experimental organisms are tomato, Arabidopsis and the diatom Phaeodactylum. His research focuses on the molecular mechanisms controlling responses to environmental signals such as light and nutrients.

During his doctoral work with Profs. Marc Van Montagu and Dirk Inzé in the Laboratorium Genetika at the University of Ghent, Belgium, he revealed the role of superoxide dismutases as a defense against environmental stress. Subsequently, his post-doctoral work with Prof. Nam-Hai Chua at The Rockefeller University in New York identified key players in light signal transduction pathways. In 1994 he established his own research group working on higher plants and marine diatoms at the Stazione Zoologica in Naples Italy and in 2002 he took up his current position at the ENS in Paris.

His group now studies the response of plants and marine diatoms to environmental signals. In plants, he identified the first high pigment gene in tomato, mutation of which causes light hypersensitivity and increased fruit phytonutrient content. The gene encodes the photomorphogenesis regulator DET1, which he found to be involved in regulating chromatin architecture, and the focus of the group is now directed towards understanding the molecular functions of DET1 and how environmental signals such as light impact genome stability in Arabidopsis. In marine diatoms he established molecular tools to assess gene function and has played a major role in coordinating the whole genome sequencing of several species. Using functional genomics he has revealed the cellular response of diatoms to nutrients such as iron and nitrogen, to different wavelengths and intesities of light, and to allelopathic infochemicals. He is one of the scientific coordinators of the Tara Oceans expedition, which left France in September 2009 for a three-year exploration of the state of microscopic life in the world's oceans using high-throughput imaging- and genomics-enabled approaches. He is member of the European Molecular Biology Organization (EMBO), associate editor of several major scientific journals, and is member of the scientific advisory boards of several internationally renowned research institutes.

Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia.

Marie Embs — 2015-02-25T09:21:28Z

In mammals, motile cilia cover many organs, such as fallopian tubes, respiratory tracts and brain ventricles. The development and function of these organs critically depend on efficient directional fluid flow ensured by the alignment of ciliary beating. To identify the mechanisms involved in this process, we analysed motile cilia of mouse brain ventricles, using biophysical and molecular approaches. Our results highlight an original orientation mechanism for ependymal cilia whereby basal bodies first dock apically with random orientations, and then reorient in a common direction through a coupling between hydrodynamic forces and the planar cell polarity (PCP) protein Vangl2, within a limited time-frame. This identifies a direct link between external hydrodynamic cues and intracellular PCP signalling. Our findings extend known PCP mechanisms by integrating hydrodynamic forces as long-range polarity signals, argue for a possible sensory role of ependymal cilia, and will be of interest for the study of fluid flow-mediated morphogenesis.

Nat Cell Biol. 2010 Apr ;12(4):341-50.

Coherent amygdalocortical theta promotes fear memory consolidation during paradoxical sleep

Marie Embs — 2015-02-25T09:16:32Z

Brain activity in sleep plays a crucial role in memory consolidation, an offline process that determines the long-term strength of memory traces. Consolidation efficacy differs across individuals, but the brain activity dynamics underlying these differences remain unknown. Here, we studied how interindividual variability in fear memory consolidation relates to neural activity in brain structures that participate in Pavlovian fear learning. From the end of training to testing 24 h later, some rats showed increased and others decreased conditioned fear responses. We found that overnight bidirectional changes in fear memory were selectively correlated with modifications in theta coherence between the amygdala, medial prefrontal cortex, and hippocampus during paradoxical sleep. Thus, our results suggest that theta coordination in the limbic system may influence interindividual differences in memory consolidation of aversive experiences.

Proc Natl Acad Sci U S A. 2010 Apr 6 ;107(14):6516-9.

L'Académie des Sciences a attribué le 29 juin 2010 à Antoine TRILLER le Prix Lamonica de neurologie

Marie Embs — 2010-06-29T11:54:00Z

Antoine TRILLER, né le 23 mai 1952, Dr en médecine et Dr ès sciences, est directeur de recherche à l'Inserm. Il a fondé et dirige l'Institut de Biologie de l'École Normale Supérieure (IBENS) de Paris, créé en 2010 avec le CNRS et l'Inserm, et y anime l'équipe « Biologie cellulaire de la synapse ». A la suite d'importantes contributions en neurobiologie fondamentale publiées dans Science (1981) et Nature (1983), il a fait des découvertes majeures concernant la dynamique des récepteurs neuronaux au niveau des synapses. Il a ainsi révélé (Nature Neuroscience 2001, Science 2003), grâce à des techniques d'imagerie moléculaire originales, que les récepteurs ne sont pas définitivement fixés au niveau de la membrane de la synapse ; ils diffusent constamment dans le plan de cette membrane, et ceci est régulé par l'activité des neurones (Neuron 2008, 2009). Ses recherches éclairent d'un jour nouveau les mécanismes physiopathologiques responsables, au niveau de la synapse, du développement de maladies neurodégénératives. Récemment (Neuron 2010), son équipe a mis en évidence un mécanisme d'accumulation anormale d'un récepteur synaptique du glutamate, ce qui pourrait ouvrir une nouvelle voie thérapeutique dans la phase initiale de la maladie d'Alzheimer.

Le projet, qu'aidera à financer le Prix Lamonica de neurologie de l'Académie des sciences porte sur le rôle pathogène des agrégats de petites protéines dans la propagation de la dégénérescence des cellules nerveuses.
Soucieux d'une recherche qui favorise la pluridisciplinarité, Antoine Triller est aussi à l'origine, avec deux Membres de l'Académie des sciences, Daniel Louvard et Jacques Prost, de la Fondation Pierre-Gilles de Gennes, créée en 2007. Contact : triller chez biologie.ens.fr