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Naihe Jing - One of the best experts on this subject based on the ideXlab platform.
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smad6 promotes neuronal differentiation in the Intermediate Zone of the dorsal neural tube by inhibition of the wnt beta catenin pathway
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Zhihui Xie, Yongfeng Chen, Ge Bai, Yue Zhu, Rui Yan, Fangzhi Tan, Ye-guang Chen, François Guillemot, Naihe JingAbstract:Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular Zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the Intermediate Zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the Intermediate Zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/β-catenin pathway. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the β-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit β-catenin–mediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription.
Zhihui Xie - One of the best experts on this subject based on the ideXlab platform.
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smad6 promotes neuronal differentiation in the Intermediate Zone of the dorsal neural tube by inhibition of the wnt beta catenin pathway
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Zhihui Xie, Yongfeng Chen, Ge Bai, Yue Zhu, Rui Yan, Fangzhi Tan, Ye-guang Chen, François Guillemot, Naihe JingAbstract:Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular Zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the Intermediate Zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the Intermediate Zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/β-catenin pathway. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the β-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit β-catenin–mediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription.
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Smad6 promotes neuronal differentiation in the Intermediate Zone of the dorsal neural tube by inhibition of the Wnt/beta-catenin pathway.
Proceedings of the National Academy of Sciences, 2011Co-Authors: Zhihui Xie, Yongfeng Chen, Ge Bai, Yue Zhu, Rui Yan, Fangzhi Tan, Ye-guang Chen, François GuillemotAbstract:Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular Zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the Intermediate Zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the Intermediate Zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/β-catenin pathway. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the β-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit β-catenin–mediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription.
François Guillemot - One of the best experts on this subject based on the ideXlab platform.
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smad6 promotes neuronal differentiation in the Intermediate Zone of the dorsal neural tube by inhibition of the wnt beta catenin pathway
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Zhihui Xie, Yongfeng Chen, Ge Bai, Yue Zhu, Rui Yan, Fangzhi Tan, Ye-guang Chen, François Guillemot, Naihe JingAbstract:Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular Zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the Intermediate Zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the Intermediate Zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/β-catenin pathway. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the β-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit β-catenin–mediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription.
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Smad6 promotes neuronal differentiation in the Intermediate Zone of the dorsal neural tube by inhibition of the Wnt/beta-catenin pathway.
Proceedings of the National Academy of Sciences, 2011Co-Authors: Zhihui Xie, Yongfeng Chen, Ge Bai, Yue Zhu, Rui Yan, Fangzhi Tan, Ye-guang Chen, François GuillemotAbstract:Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular Zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the Intermediate Zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the Intermediate Zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/β-catenin pathway. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the β-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit β-catenin–mediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription.
Norbert König - One of the best experts on this subject based on the ideXlab platform.
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molecular interaction between projection neuron precursors and invading interneurons via stromal derived factor 1 cxcl12 cxcr4 signaling in the cortical subventricular Zone Intermediate Zone
The Journal of Neuroscience, 2006Co-Authors: Mariecatherine Tiveron, Norbert König, Mireille Rossel, Barbara Moepps, Yong Li Zhang, Ralph Seidenfaden, Jack Favor, Harold CremerAbstract:Most cortical interneurons are generated in the subpallial ganglionic eminences and migrate tangentially to their final destinations in the neocortex. Within the cortex, interneurons follow mainly stereotype routes in the subventricular Zone/Intermediate Zone (SVZ/IZ) and in the marginal Zone. It has been suggested that interactions between invading interneurons and locally generated projection neurons are implicated in the temporal and spatial regulation of the invasion process. However, so far experimental evidence for such interactions is lacking. We show here that the chemokine stromal-derived factor 1 (SDF-1; CXCL12) is expressed in the main invasion route for cortical interneurons in the SVZ/IZ. Most SDF-1-positive cells are proliferating and express the homeodomain transcription factors Cux1 and Cux2. Using MASH-1 mutant mice in concert with the interneuron marker DLX, we exclude that interneurons themselves produce the chemokine in an autocrine manner. We conclude that the SDF-1-expressing cell population represents the precursors of projection neurons during their transition and amplification in the SVZ/IZ. Using mice lacking the SDF-1 receptor CXCR4 or Pax6, we demonstrate that SDF-1 expression in the cortical SVZ/IZ is essential for recognition of this pathway by interneurons. These results represent the first evidence for a molecular interaction between precursors of projection neurons and invading interneurons during corticogenesis.
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Stromal cell-derived factor-1 (SDF-1) expression in embryonic mouse cerebral cortex starts in the Intermediate Zone close to the pallial-subpallial boundary and extends progressively towards the cortical hem
Gene Expression Patterns, 2005Co-Authors: Dorothée Daniel, Mireille Rossel, Tatsunori Seki, Norbert KönigAbstract:We describe the onset and the expansion of stromal cell-derived factor 1 (SDF-1) expression in the Intermediate Zone of embryonic mouse cerebral cortex between embryonic days (E)11.5 and 18.5, and on postnatal day 1. Using in situ hybridisation with a digoxigenin-labeled probe, SDF-1 mRNA was detectable by E 12.5 in a small area of the Intermediate Zone just dorsal to the pallial-subpallial boundary. During the following days, SDF-1 expression extended towards the dorso-lateral pallium, and then the hippocampus and cortical hem. The position of the SDF-1 positive cells within the Intermediate Zone was closely correlated with the stream of tangentially migrating cells carrying the polysialylated form of neural cell adhesion molecule (PSA-NCAM). However, whereas these cells form a ventro-dorsal stream passing from the subpallium into the pallium, SDF-1 was not detectable on the ventral side of the pallial-subpallial boundary at any of the developmental stages studied. By E 16.5, the intensity of SDF-1 hybridisation signal in the Intermediate Zone decreased, to become undetectable by E 18.5.
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AMPA-evoked ion influx is strongest in tangential neurons of the rat neocortical Intermediate Zone close to the front of the migratory stream.
Developmental Dynamics, 2003Co-Authors: Sylvie Poluch, Mireille Rossel, Norbert KönigAbstract:In addition to the classically described radially migrating neurons, embryonic cortical areas receive neurons originating from the basal ganglia. One of the migration routes is in the Intermediate Zone. The front of this migration moves toward the hippocampus synchronously with the edge of the dorsally extending cortical plate. We investigated whether cells close to the front have specific properties compared with those at less advanced positions. Activation of AMPA receptors in the presence of cobalt showed that a strong influx of divalent cations could be triggered in front cells by low agonist concentration, whereas the less advanced cells needed a higher concentration to incorporate detectable amounts of cobalt. As shown by in situ hybridization, this discrepancy was not due to differential expression of GluR-2 (known to reduce permeability for divalent cations). In vivo, release of an endogenous agonist presumably affects more, or differently, the tangential cells close to the front.
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AMPA receptor activation induces GABA release from neurons migrating tangentially in the Intermediate Zone of embryonic rat neocortex.
European Journal of Neuroscience, 2002Co-Authors: Sylvie Poluch, Norbert KönigAbstract:In the Intermediate Zone of the embryonic rodent neocortex, neurons migrating tangentially from the basal ganglia express both functional amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors and gamma-aminobutyric acid (GABA). To test the hypothesis of GABA release triggered by AMPA receptor activation, we used whole-hemisphere cultures prepared from rat embryos (day 15). We observed a marked decrease in the number of detectable GABA-positive cells in the Intermediate Zone after exposure to T-AMPA. This effect was blocked by coapplying GYKI 53655, an AMPA receptor antagonist. The decrease in GABA immunolabelling induced by T-AMPA did not require extracellular calcium. In contrast, it was abolished after sodium substitution by choline, or after coapplication of nipecotic acid, a GABA transporter inhibitor. Exposure to high potassium reduced the number of detectable GABA-positive cells. These results are compatible with carrier-mediated GABA release consecutive to sodium influx. GABA released from neurons migrating tangentially in the Intermediate Zone after AMPA receptor activation may influence neighbouring elements including radially migrating postmitotic neurons, proliferating progenitors and possibly the tangential cells themselves.
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AMPA receptor activation leads to neurite retraction in tangentially migrating neurons in the Intermediate Zone of the embryonic rat neocortex.
Journal of Neuroscience Research, 2001Co-Authors: Sylvie Poluch, M.j. Drian, Micheline Durand, Catherine Astier, Yves Benyamin, Norbert KönigAbstract:In rat (König et al. [1998] 28th Annual Meeting of the Society of Neuroscience, Los Angeles. 24:314.6) and mouse (Métin et al. [2000] J. Neurosci. 20:696-708), neurons migrating tangentially in the Intermediate Zone (IZ) of the neocortical anlage express functional AMPA receptors permeable to calcium. The role of these receptors is as yet unknown. We exposed organotypic cultures of rat telencephalon (embryonic day 15) to AMPA receptor agonists or antagonists, and analyzed the effects of these treatments on cells in the IZ labeled with antibodies against the isoforms a, b and c of microtubule associated protein 2 (MAP2) and the polysialylated neural cell adhesion molecule (PSA-NCAM). The presence of functional AMPA receptors permeable to calcium was checked by cobalt-loading. After exposure to AMPA alone for at least 6 hr, we observed a significant increase in the number of rounded, MAP2 positive cells in the IZ close to the migratory front. When AMPA was combined with cyclothiazide, the increase was already significant after 3 hr. These effects were dose-dependent and could be partially or totally blocked by DNQX or GYKI 53655 respectively, that suggests that they are mediated by AMPA receptors. Paracrine AMPA receptor activation might participate, together with other signals, in guiding the migratory stream, or provide stop signals for migrating cells.
Rui Yan - One of the best experts on this subject based on the ideXlab platform.
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smad6 promotes neuronal differentiation in the Intermediate Zone of the dorsal neural tube by inhibition of the wnt beta catenin pathway
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Zhihui Xie, Yongfeng Chen, Ge Bai, Yue Zhu, Rui Yan, Fangzhi Tan, Ye-guang Chen, François Guillemot, Naihe JingAbstract:Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular Zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the Intermediate Zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the Intermediate Zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/β-catenin pathway. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the β-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit β-catenin–mediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription.
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Smad6 promotes neuronal differentiation in the Intermediate Zone of the dorsal neural tube by inhibition of the Wnt/beta-catenin pathway.
Proceedings of the National Academy of Sciences, 2011Co-Authors: Zhihui Xie, Yongfeng Chen, Ge Bai, Yue Zhu, Rui Yan, Fangzhi Tan, Ye-guang Chen, François GuillemotAbstract:Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular Zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the Intermediate Zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the Intermediate Zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/β-catenin pathway. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the β-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit β-catenin–mediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription.