References of "Malgrange, Brigitte"
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See detailIn vivo protection of spiral ganglion neurons by bryostatin 1: preliminary results
POIRRIER, Anne-Lise ULg; Van Den Ackerveken, Priscilla ULg; Defourny, Jean et al

in Advances in Cellular and Molecular Otolaryngology (2013), 1

Background: We aim to demonstrate the effect of bryostatin 1, a macrocyclic lactone that activates protein kinase C, on spiral ganglion neurons (SGNs) of adult guinea pigs deafened by aminoglycoside ... [more ▼]

Background: We aim to demonstrate the effect of bryostatin 1, a macrocyclic lactone that activates protein kinase C, on spiral ganglion neurons (SGNs) of adult guinea pigs deafened by aminoglycoside. Methodology: Twenty-one guinea pigs were deafened by the aminoglycoside gentamicin and then treated by continuous infusion of experimental molecule for 1 month. The experimental molecule was bryostatin 1, artificial perilymph (negative control), or neurotrophins and an apoptosis inhibitor (positive control). Neuronal density in the spiral ganglia was quantified. Results: Bryostatin 1 protected SGNs after a gentamicin challenge. Conclusions: Bryostatin 1 has a neuroprotective effect when administered continuously at low doses in adult guinea pigs. [less ▲]

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See detailEphrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells.
Defourny, Jean; Poirrier, Anne-Lise; Lallemend, Francois et al

in Nature Communications (2013), 4

Hearing requires an optimal afferent innervation of sensory hair cells by spiral ganglion neurons in the cochlea. Here we report that complementary expression of ephrin-A5 in hair cells and EphA4 receptor ... [more ▼]

Hearing requires an optimal afferent innervation of sensory hair cells by spiral ganglion neurons in the cochlea. Here we report that complementary expression of ephrin-A5 in hair cells and EphA4 receptor among spiral ganglion neuron populations controls the targeting of type I and type II afferent fibres to inner and outer hair cells, respectively. In the absence of ephrin-A5 or EphA4 forward signalling, a subset of type I projections aberrantly overshoot the inner hair cell layer and invade the outer hair cell area. Lack of type I afferent synapses impairs neurotransmission from inner hair cells to the auditory nerve. By contrast, radial shift of type I projections coincides with a gain of presynaptic ribbons that could enhance the afferent signalling from outer hair cells. Ephexin-1, cofilin and myosin light chain kinase act downstream of EphA4 to induce type I spiral ganglion neuron growth cone collapse. Our findings constitute the first identification of an Eph/ephrin-mediated mutual repulsion mechanism responsible for specific sorting of auditory projections in the cochlea. [less ▲]

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See detailUnravelling the roles of lysine acetylation by Elp3 during inner ear development
Mateo Sanchez, Susana ULg; Delacroix, Laurence ULg; Laguesse, Sophie ULg et al

Poster (2012, May 04)

The inner ear is composed of a vestibular part that controls balance, and the cochlea, which is dedicated to hearing. In both parts of the inner ear, sensory epithelia comprise supporting cells ... [more ▼]

The inner ear is composed of a vestibular part that controls balance, and the cochlea, which is dedicated to hearing. In both parts of the inner ear, sensory epithelia comprise supporting cells surrounding the sensory hair cells. These cells bear at their apical surface a staircase-structured hair bundle, consisting of multiple rows of actin-based stereocilia and a single tubulin-based kinocilium. This hair bundle allows the transduction from mechanical stimuli, initiated by sound or gravitational changes, to electrical signals that will then be transmitted by neurons from the spiral ganglion (innervating hair cells of the cochlea) or the vestibular ganglion. The inner ear organogenesis requires a tightly regulated transcriptional program that can be affected by post-transcriptional and post-translational modifications among which lysine acetylation. Given the importance of acetylation homeostasis in controlling developmental processes, we planned to investigate its role in inner ear formation and focused our attention on Elp3 acetyl-transferase, a member of the Elongator complex recently implicated in neurogenesis. First, we have analysed Elp3 expression by in situ hybridization on wild type mice at different developmental stages (from E11.5 until P6) and showed that it was expressed in the entire early otocyst at E11.5 and persisted later in the sensory epithelium of the cochlea (the organ of Corti), in the stria vascularis and in the vestibule. To study the functional consequences of protein acetylation by the Elongator complex in the inner ear, we studied conditional knock-out mice (Elp3 cKO) in which Elp3 is depleted from the otic vesicle at E8.5. These mice, at stage P15, showed obvious balance dysfunction that was confirmed by a complete battery of behavioural tests: stereotyped circling ambulation, head bobbing, retropulsion, and absence of reaching response in the tail-hanging test. Unfortunately, the Elp3 cKO mice die before the onset of hearing, thus precluding any evaluation of hearing disorders. Balance defects in mice depleted for Elp3 is not due to vestibular structural abnormalities, since paint-filling experiments showed a normal inner ear anatomy compared to wild type mice. Moreover, immunostainings in the vestibule and in the organ of Corti indicated that cell patterning was not impaired in the absence of Elp3 since specialised cells are present and correctly organised at embryonic day E18.5 and later on. However, we were able to detect some defaults in hair cell bundle integrity and orientation in the auditory portion of inner ear from Elp3 cKO mice. We were also able to demonstrate an increased level of apoptosis in the Elp3 cKO spiral ganglion at E14.5 leading to a reduced number of fibers innervating the cochlear hair cells at P0 and P15. In conclusion, we have confirmed the expression of Elp3 in the inner ear and pointed out a role for this acetyl-transferase in balance function. Our results clearly show the implication of Elp3 in ciliogenesis, hair cell innervation and neuronal survival and we plan to go deeper in the mechanisms involved through the identification of the proteins acetylated by Elp3. [less ▲]

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See detailHuntington’s Disease: From the Physiological Function of Huntingtin to the Disease
Borgs, Laurence ULg; Godin, Juliette ULg; Malgrange, Brigitte ULg et al

in Huntington's Disease - Core Concepts and Current Advances (2012)

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See detailCortical interneurons tangential migration : p27(Kip1) as a novel master regulator.
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Poster (2012)

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See detailp27(Kip1) as a master regulator of cortical neuron migration.
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Poster (2012)

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See detailp27(Kip1) as a master regulator of cortical neuron migration.
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Poster (2012)

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See detailCycling or not cycling: cell cycle regulatory molecules and adult neurogenesis.
Beukelaers, Pierre ULg; Vandenbosch, Renaud ULg; Caron, Nicolas ULg et al

in Cellular and Molecular Life Sciences : CMLS (2012), 69(9), 1493-1503

The adult brain most probably reaches its highest degree of plasticity with the lifelong generation and integration of new neurons in the hippocampus and olfactory system. Neural precursor cells (NPCs ... [more ▼]

The adult brain most probably reaches its highest degree of plasticity with the lifelong generation and integration of new neurons in the hippocampus and olfactory system. Neural precursor cells (NPCs) residing both in the subgranular zone of the dentate gyrus and in the subventricular zone of the lateral ventricles continuously generate neurons that populate the dentate gyrus and the olfactory bulb, respectively. The regulation of NPC proliferation in the adult brain has been widely investigated in the past few years. Yet, the intrinsic cell cycle machinery underlying NPC proliferation remains largely unexplored. In this review, we discuss the cell cycle components that are involved in the regulation of NPC proliferation in both neurogenic areas of the adult brain. [less ▲]

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See detailMicroRNAs tune cerebral cortical neurogenesis.
Volvert, M.-L.; Rogister, F.; Moonen, Gustave ULg et al

in Cell Death & Differentiation (2012), 19(10), 1573-81

MicroRNAs (miRNAs) are non-coding RNAs that promote post-transcriptional silencing of genes involved in a wide range of developmental and pathological processes. It is estimated that most protein-coding ... [more ▼]

MicroRNAs (miRNAs) are non-coding RNAs that promote post-transcriptional silencing of genes involved in a wide range of developmental and pathological processes. It is estimated that most protein-coding genes harbor miRNA recognition sequences in their 3' untranslated region and are thus putative targets. While functions of miRNAs have been extensively characterized in various tissues, their multiple contributions to cerebral cortical development are just beginning to be unveiled. This review aims to outline the evidence collected to date demonstrating a role for miRNAs in cerebral corticogenesis with a particular emphasis on pathways that control the birth and maturation of functional excitatory projection neurons. [less ▲]

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See detailp27(Kip1) Is a Microtubule-Associated Protein that Promotes Microtubule Polymerization during Neuron Migration.
Godin, Juliette ULg; Thomas, Noemie; Laguesse, Sophie ULg et al

in Developmental Cell (2012), 23(4), 729-44

The migration of cortical interneurons is characterized by extensive morphological changes that result from successive cycles of nucleokinesis and neurite branching. Their molecular bases remain elusive ... [more ▼]

The migration of cortical interneurons is characterized by extensive morphological changes that result from successive cycles of nucleokinesis and neurite branching. Their molecular bases remain elusive, and the present work describes how p27(Kip1) controls cell-cycle-unrelated signaling pathways to regulate these morphological remodelings. Live imaging reveals that interneurons lacking p27(Kip1) show delayed tangential migration resulting from defects in both nucleokinesis and dynamic branching of the leading process. At the molecular level, p27(Kip1) is a microtubule-associated protein that promotes polymerization of microtubules in extending neurites, thereby contributing to tangential migration. Furthermore, we show that p27(Kip1) controls actomyosin contractions that drive both forward translocation of the nucleus and growth cone splitting. Thus, p27(Kip1) cell-autonomously controls nucleokinesis and neurite branching by regulating both actin and microtubule cytoskeletons. [less ▲]

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See detailp27(Kip1) as a master regulator of cortical neuron migration
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Scientific conference (2011, June)

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See detailComparaison des outils bibliographiques et bibliométriques Web of Science et Scopus : rapport du groupe de réflexion mis en place par la Bibliothèque Interuniversitaire de la Communauté française de Belgique (BICfB)
Lerinckx, Dominique; Baguet, Muriel; Renaville, François ULg et al

Report (2011)

Depuis 2002, l'ensemble des membres de la BICfB souscrivent au Web of Science (WoS) de Thomson Reuters, plus précisément aux sous-bases Science Citation Index (SCI), Social Sciences Citation Index (SCCI ... [more ▼]

Depuis 2002, l'ensemble des membres de la BICfB souscrivent au Web of Science (WoS) de Thomson Reuters, plus précisément aux sous-bases Science Citation Index (SCI), Social Sciences Citation Index (SCCI) et Arts and Humanities Citation Index (A&HCI). Web of Science, partie du Web of Knowledge (WoK), est une base de données bibliographiques et d'analyse de citations renommée, au départ unique en son genre. Avec le Journal Citation Reports (JCR), elle est également beaucoup utilisée comme base de référence dans l'évaluation des chercheurs et de la recherche. En 2004, deux ressources concurrentes ont vu le jour. Il s'agit de Google Scholar (gratuit mais n'offrant pas autant de fonctionnalités) et de Scopus, un produit Elsevier. Aussi, lors de l'Assemblée générale de la BICfB du 4 mai 2010, les institutions ont décidé de constituer un groupe de réflexion interuniversitaire composé de membres issus des conseils ou administrations de la recherche, de bibliothèques et de représentants du F.R.S.-FNRS afin de comparer en profondeur ces outils. Ce rapport, présenté lors de l'AG du 7 juin 2011 de la BICfB, est le fruit du travail du groupe de réflexion. [less ▲]

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See detailSpatio-temporal localization of the cytoskeleton during auditory organ development in mammalia
Johnen, Nicolas ULg; Thelen, Nicolas ULg; Cloes, Marie ULg et al

Poster (2011, March 31)

The auditory organ, the organ of Corti (OC), is a highly specialized structure composed by specific cellular types. The sensory cells (HC) are characterized by stereocilia at their apex and are necessary ... [more ▼]

The auditory organ, the organ of Corti (OC), is a highly specialized structure composed by specific cellular types. The sensory cells (HC) are characterized by stereocilia at their apex and are necessary for the sound perception. Theses cells are supported by supporting cells. Based on their morphology and physiology, at least four types of supporting cells (SC) can be identified in the OC: inner and outer pillar cells (PC), phalangeal cell and Deiter’s cells. Sensory and supporting cells possess characteristic cytoskeleton proteins in direct relation with their morphological features and their development. Indeed, this organ had morphological changes such as the setting up of the sensory epithelium after the birth or the openings of the Corti’s tunnel at P8 and of the Nuel’s spaces at P10. In the present study, by using confocal microscopy, we investigated the spatio-temporal localization of the three cellular cytoskeletal filaments : microtubules (β-1, 2, 3, 4-tubulin), microfilaments (cytoplasmic β- and γ-actin) and intermediate filaments (CK4, 5, 7, 8, CKpan and vimentin) during the development of the OC in rat from the embryonic day 18 (E18) to the post-natal day 25 (P25). The immunolabellings indicated clearly that β-1, 2, 3-tubulins were only present the SC and nervous fibers during development whereas β-4-tubulin was found firstly in the HC and then in the SC. The two actin-isotypes were detected in the HC apex but were also seen in the PC from P8 to P25 for β-actin isoform and in the basal membrane from E18 to P8 for the γ-actin isoform. All intermediate filament proteins were only found in the SC, especially between P8 and P12. Our results show that the localization of the cytoskeleton proteins during the auditory organ development depends on the cellular type and the developmental stage. A profound modification of cytoskeleton occurs between P8 and P12. [less ▲]

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See detailDistribution of glycogen during the development of the organ of Corti
Thelen, Nicolas ULg; Cloes, Marie ULg; Johnen, Nicolas ULg et al

Poster (2011, January 31)

Although the structure of the auditory organ in mature mammals, the organ of Corti, is clearly established, its development is far from being elucidated. Using cytochemical methods at the light and ... [more ▼]

Although the structure of the auditory organ in mature mammals, the organ of Corti, is clearly established, its development is far from being elucidated. Using cytochemical methods at the light and electron microscope levels, we examined the spatiotemporal distribution of polysaccharides during the development of the organ of Corti in rats from embryonic day 16 (E16) to postnatal day 15 (P15). At E16, small polysaccharide inclusions were detected in the cytoplasm of the future inner pillar cells by electron microscope only. These inclusions became obvious at the light microscope level at E17. At E19, the polysaccharide deposits were important within the inner pillar cells and they arose in the Hensen cells cytoplasm. Polysaccharide accumulations also appeared in the outer pillar cells and the Deiters cells from P3-P4. As the organ of Corti developed, the amount of polysaccharide inclusions within the inner and outer pillar cells decreased. At P15, large amount of polysaccharide deposits were visible in the Deiters cells whereas they had almost disappeared from the inner and outer pillar cells. Finally, we showed that the polysaccharide deposits present in the developing organ of Corti are PAS-positive and can be digested with a salivary amylase, suggesting that they are essentially constituted of glycogen. [less ▲]

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See detailCdk6-dependent regulation of g(1) length controls adult neurogenesis.
Beukelaers, Pierre; Vandenbosch, Renaud ULg; Caron, Nicolas ULg et al

in Stem Cells (2011), 29(4), 713-24

The presence of neurogenic precursors in the adult mammalian brain is now widely accepted, but the mechanisms coupling their proliferation with the onset of neuronal differentiation remain unknown. Here ... [more ▼]

The presence of neurogenic precursors in the adult mammalian brain is now widely accepted, but the mechanisms coupling their proliferation with the onset of neuronal differentiation remain unknown. Here, we unravel the major contribution of the G(1) regulator cyclin-dependent kinase 6 (Cdk6) to adult neurogenesis. We found that Cdk6 was essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Specifically, Cdk6 deficiency prevents the expansion of neuronally committed precursors by lengthening G(1) phase duration, reducing concomitantly the production of newborn neurons. Altogether, our data support G(1) length as an essential regulator of the switch between proliferation and neuronal differentiation in the adult brain and Cdk6 as one intrinsic key molecular regulator of this process. STEM Cells 2011;29:713-724. [less ▲]

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See detailCdk2 loss accelerates precursor differentiation and remyelination in the adult central nervous system.
Caillava, Céline; Vandenbosch, Renaud ULg; Jablonska, Beata et al

in Journal of Cell Biology (2011), 193(2), 397-407

The specific functions of intrinsic regulators of oligodendrocyte progenitor cell (OPC) division are poorly understood. Type 2 cyclin-dependent kinase (Cdk2) controls cell cycle progression of OPCs, but ... [more ▼]

The specific functions of intrinsic regulators of oligodendrocyte progenitor cell (OPC) division are poorly understood. Type 2 cyclin-dependent kinase (Cdk2) controls cell cycle progression of OPCs, but whether it acts during myelination and repair of demyelinating lesions remains unexplored. Here, we took advantage of a viable Cdk2(-/-) mutant mouse to investigate the function of this cell cycle regulator in OPC proliferation and differentiation in normal and pathological conditions. During central nervous system (CNS) development, Cdk2 loss does not affect OPC cell cycle, oligodendrocyte cell numbers, or myelination. However, in response to CNS demyelination, it clearly alters adult OPC renewal, cell cycle exit, and differentiation. Importantly, Cdk2 loss accelerates CNS remyelination of demyelinated axons. Thus, Cdk2 is dispensable for myelination but is important for adult OPC renewal, and could be one of the underlying mechanisms that drive adult progenitors to differentiate and thus regenerate myelin. [less ▲]

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See detailUsing human pluripotent stem cells to untangle neurodegenerative disease mechanisms
Malgrange, Brigitte ULg; Borgs, Laurence ULg; Grobarczyk, Benjamin ULg et al

in Cellular and Molecular Life Sciences : CMLS (2011), 68(4), 635-49

Human pluripotent stem cells, including embryonic (hES) and induced pluripotent stem cells (hiPS), retain the ability to self-renew indefinitely, while maintaining the capacity to differentiate into all ... [more ▼]

Human pluripotent stem cells, including embryonic (hES) and induced pluripotent stem cells (hiPS), retain the ability to self-renew indefinitely, while maintaining the capacity to differentiate into all cell types of the nervous system. While human pluripotent cell-based therapies are unlikely to arise soon, these cells can currently be used as an inexhaustible source of committed neurons to perform high-throughput screening and safety testing of new candidate drugs. Here, we describe critically the available methods and molecular factors that are used to direct the differentiation of hES or hiPS into specific neurons. In addition, we discuss how the availability of patient-specific hiPS offers a unique opportunity to model inheritable neurodegenerative diseases and untangle their pathological mechanisms, or to validate drugs that would prevent the onset or the progression of these neurological disorders. [less ▲]

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See detailStructure and development of cochlear afferent innervation in mammals.
Defourny, Jean ULg; Lallemend, Francois; Malgrange, Brigitte ULg

in American Journal of Physiology - Cell Physiology (2011), 301(4), 750-61

In mammals, sensorineural deafness results from damage to the auditory receptors of the inner ear, the nerve pathways to the brain or the cortical area that receives sound information. In this review, we ... [more ▼]

In mammals, sensorineural deafness results from damage to the auditory receptors of the inner ear, the nerve pathways to the brain or the cortical area that receives sound information. In this review, we first focused on the cellular and molecular events taking part to spiral ganglion axon growth, extension to the organ of Corti, and refinement. In the second half, we considered the functional maturation of synaptic contacts between sensory hair cells and their afferent projections. A better understanding of all these processes could open insights into novel therapeutic strategies aimed to re-establish primary connections from sound transducers to the ascending auditory nerve pathways. [less ▲]

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