References of "Nguyen, Laurent"
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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 detailDERP6 (ELP5) and C3ORF75 (ELP6) regulate tumorigenicity and migration of melanoma cells as subunits of Elongator
Close, Pierre ULg; Gillard, Magali; Ladang, Aurélie ULg et al

in Journal of Biological Chemistry (2012)

The Elongator complex is composed of 6 subunits (Elp1-Elp6) and promotes RNAPII transcript elongation through histone acetylation in the nucleus as well as tRNA modification in the cytoplasm. This ... [more ▼]

The Elongator complex is composed of 6 subunits (Elp1-Elp6) and promotes RNAPII transcript elongation through histone acetylation in the nucleus as well as tRNA modification in the cytoplasm. This acetyltransferase complex directly or indirectly regulates numerous biological processes ranging from exocytosis and resistance to heat shock in yeast to cell migration and neuronal differentiation in higher eukaryotes. The identity of human ELP1 through ELP4 has been reported but human ELP5 and ELP6 have remained uncharacterized. Here, we report that DERP6 (ELP5) and C3ORF75 (ELP6) encode these subunits of human Elongator. We further investigated the importance and function of these two subunits by a combination of biochemical analysis and cellular assays. Our results show that DERP6/ELP5 is required for the integrity of Elongator and directly connects ELP3 to ELP4. Importantly, the migration and tumorigenicity of melanomaderived cells are significantly decreased upon Elongator depletion through ELP1 or ELP3. Strikingly, DERP6/ELP5 and C3ORF75/ELP6-depleted melanoma cells have similar defects, further supporting the idea that DERP6/ELP5 and C3ORF75/ELP6 are essential for Elongator function. Together, our data identify DERP6/ELP5 and C3ORF75/ELP6 as key players for migration, invasion and tumorigenicity of melanoma cells, as integral subunits of Elongator. [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 detailGlycine receptor activation controls interneuron migration by affecting nuclear translocation and myosin phosphorylation
Avila Macaya, Ariel Salvatore ULg; Nguyen, Laurent ULg

Poster (2012)

Previous studies have described the presence of glycine receptor mRNA during early stages of embryonic cortex development. Here, we have tested the functionality of those receptors in migratory ... [more ▼]

Previous studies have described the presence of glycine receptor mRNA during early stages of embryonic cortex development. Here, we have tested the functionality of those receptors in migratory interneurons and demonstrated their involvement in the control of cell migration. We suggest a mechanism whereby activation of glycine receptors during tangential migration activates voltage gated calcium channels and favors influx of calcium that ultimately affect myosin II activity, a mechanism that fine tune nuclear translocation and thus migration speed. [less ▲]

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See detailGlycine receptor activation influences early cortical development
Avila Macaya, Ariel Salvatore ULg; Nguyen, Laurent ULg

Poster (2011, July 14)

The strychnine-sensitive glycine receptor (GlyR) is a member of the ligand-gated ion channel superfamily. In the adult, the GlyR is known to mediate fast inhibitory neurotransmission in the spinal cord ... [more ▼]

The strychnine-sensitive glycine receptor (GlyR) is a member of the ligand-gated ion channel superfamily. In the adult, the GlyR is known to mediate fast inhibitory neurotransmission in the spinal cord and in the brainstem. The GlyR has also been described in the embryonic cortex after embryonic day 19 (E19) (Flint et al., 1998) where it could participate in developmental processes, but its presence at earlier stages has not been documented. Since other neurotransmitter systems, i.e. GABA and its receptors, are known to be potent signals that control corticogenesis (Nguyen et al., 2001; Ik-Tsen et al., 2007), we wondered if glycine and its GlyR could also fulfill such a function. In this study, we analyze GlyR expression and its physiological function in the early development of the cortex using in vitro cultures of embryonic day 13 slices, patch-clamp and immunocytochemistry. [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 detailPhosphorylation of SCG10/stathmin-2 determines multipolar stage exit and neuronal migration rate
Westerlund, N.; Zdrojewska, J.; Padzik, A. et al

in Nature Neuroscience (2011)

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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 detailThe glycine receptor is functionally expressed in migratory interneurons and influences early cortical development
Avila Macaya, Ariel Salvatore ULg; Nguyen, Laurent ULg

Poster (2011)

The strychnine-sensitive glycine receptor (GlyR) is a member of the ligand-gated ion channel superfamily. In the adult, the GlyR is known to mediate fast inhibitory neurotransmission in the spinal cord ... [more ▼]

The strychnine-sensitive glycine receptor (GlyR) is a member of the ligand-gated ion channel superfamily. In the adult, the GlyR is known to mediate fast inhibitory neurotransmission in the spinal cord and in the brainstem. The GlyR has also been described in the embryonic cortex after embryonic day 19 (E19) (Flint et al., 1998) where it could participate in developmental processes, but its presence at earlier stages has not been documented. Since other neurotransmitter systems, i.e. GABA and its receptors, are known to be potent signals that control corticogenesis (Nguyen et al., 2001; Ik-Tsen et al., 2007), we wondered if glycine and its GlyR could also fulfill such a function. In this study, we analyze GlyR expression and its physiological function in the early development of the cortex using in vitro cultures of embryonic day 13 slices, patch-clamp, two photon microscopy and immunocytochemistry. [less ▲]

Detailed reference viewed: 18 (1 ULg)