The Experts below are selected from a list of 52542 Experts worldwide ranked by ideXlab platform
Sergej Nowoshilow - One of the best experts on this subject based on the ideXlab platform.
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planar Cell polarity mediated induction of Neural Stem Cell expansion during axolotl spinal cord regeneration
eLife, 2015Co-Authors: Aida Rodrigo Albors, Akira Tazaki, Fabian Rost, Sergej NowoshilowAbstract:Axolotls are uniquely able to mobilize Neural Stem Cells to regenerate all missing regions of the spinal cord. How a Neural Stem Cell under homeostasis converts after injury to a highly regenerative Cell remains unknown. Here, we show that during regeneration, axolotl Neural Stem Cells repress neurogenic genes and reactivate a transcriptional program similar to embryonic neuroepithelial Cells. This dedifferentiation includes the acquisition of rapid Cell cycles, the switch from neurogenic to proliferative divisions, and the re-expression of planar Cell polarity (PCP) pathway components. We show that PCP induction is essential to reorient mitotic spindles along the anterior-posterior axis of elongation, and orthogonal to the Cell apical-basal axis. Disruption of this property results in premature neurogenesis and halts regeneration. Our findings reveal a key role for PCP in coordinating the morphogenesis of spinal cord outgrowth with the switch from a homeostatic to a regenerative Stem Cell that restores missing tissue.
Yanhong Shi - One of the best experts on this subject based on the ideXlab platform.
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orphan nuclear receptor tlx activates wnt beta catenin signalling to stimulate Neural Stem Cell proliferation and self renewal
Nature Cell Biology, 2010Co-Authors: Guoqiang Sun, Chunnian Zhao, Su Yang, Ronald M Evans, Fred H Gage, Yanhong ShiAbstract:The nuclear receptor TLX (also known as NR2E1) is essential for adult Neural Stem Cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse Neural Stem Cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult Neural Stem Cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote Neural Stem Cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased Cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B Neural Stem Cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of Neural Stem Cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in Neural Stem Cell proliferation. Lentiviral transduction of an active beta-catenin increased Cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate Neural Stem Cell proliferation and self-renewal. Moreover, this study suggests that Neural Stem Cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.
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orphan nuclear receptor tlx recruits histone deacetylases to repress transcription and regulate Neural Stem Cell proliferation
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Guoqiang Sun, Ronald M Evans, Yanhong ShiAbstract:TLX is a transcription factor that is essential for Neural Stem Cell proliferation and self-renewal. However, the molecular mechanism of TLX-mediated Neural Stem Cell proliferation and self-renewal is largely unknown. We show here that TLX recruits histone deacetylases (HDACs) to its downstream target genes to repress their transcription, which in turn regulates Neural Stem Cell proliferation. TLX interacts with HDAC3 and HDAC5 in Neural Stem Cells. The HDAC5-interaction domain was mapped to TLX residues 359–385, which contains a conserved nuclear receptor–coregulator interaction motif IXXLL. Both HDAC3 and HDAC5 have been shown to be recruited to the promoters of TLX target genes along with TLX in Neural Stem Cells. Recruitment of HDACs led to transcriptional repression of TLX target genes, the cyclin-dependent kinase inhibitor, p21CIP1/WAF1(p21), and the tumor suppressor gene, pten. Either inhibition of HDAC activity or knockdown of HDAC expression led to marked induction of p21 and pten gene expression and dramatically reduced Neural Stem Cell proliferation, suggesting that the TLX-interacting HDACs play an important role in Neural Stem Cell proliferation. Moreover, expression of a TLX peptide containing the minimal HDAC5 interaction domain disrupted the TLX–HDAC5 interaction. Disruption of this interaction led to significant induction of p21 and pten gene expression and to dramatic inhibition of Neural Stem Cell proliferation. Taken together, these findings demonstrate a mechanism for Neural Stem Cell proliferation through transcriptional repression of p21 and pten gene expression by TLX–HDAC interactions.
Aida Rodrigo Albors - One of the best experts on this subject based on the ideXlab platform.
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planar Cell polarity mediated induction of Neural Stem Cell expansion during axolotl spinal cord regeneration
eLife, 2015Co-Authors: Aida Rodrigo Albors, Akira Tazaki, Fabian Rost, Sergej NowoshilowAbstract:Axolotls are uniquely able to mobilize Neural Stem Cells to regenerate all missing regions of the spinal cord. How a Neural Stem Cell under homeostasis converts after injury to a highly regenerative Cell remains unknown. Here, we show that during regeneration, axolotl Neural Stem Cells repress neurogenic genes and reactivate a transcriptional program similar to embryonic neuroepithelial Cells. This dedifferentiation includes the acquisition of rapid Cell cycles, the switch from neurogenic to proliferative divisions, and the re-expression of planar Cell polarity (PCP) pathway components. We show that PCP induction is essential to reorient mitotic spindles along the anterior-posterior axis of elongation, and orthogonal to the Cell apical-basal axis. Disruption of this property results in premature neurogenesis and halts regeneration. Our findings reveal a key role for PCP in coordinating the morphogenesis of spinal cord outgrowth with the switch from a homeostatic to a regenerative Stem Cell that restores missing tissue.
Akira Tazaki - One of the best experts on this subject based on the ideXlab platform.
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planar Cell polarity mediated induction of Neural Stem Cell expansion during axolotl spinal cord regeneration
eLife, 2015Co-Authors: Aida Rodrigo Albors, Akira Tazaki, Fabian Rost, Sergej NowoshilowAbstract:Axolotls are uniquely able to mobilize Neural Stem Cells to regenerate all missing regions of the spinal cord. How a Neural Stem Cell under homeostasis converts after injury to a highly regenerative Cell remains unknown. Here, we show that during regeneration, axolotl Neural Stem Cells repress neurogenic genes and reactivate a transcriptional program similar to embryonic neuroepithelial Cells. This dedifferentiation includes the acquisition of rapid Cell cycles, the switch from neurogenic to proliferative divisions, and the re-expression of planar Cell polarity (PCP) pathway components. We show that PCP induction is essential to reorient mitotic spindles along the anterior-posterior axis of elongation, and orthogonal to the Cell apical-basal axis. Disruption of this property results in premature neurogenesis and halts regeneration. Our findings reveal a key role for PCP in coordinating the morphogenesis of spinal cord outgrowth with the switch from a homeostatic to a regenerative Stem Cell that restores missing tissue.
Guoqiang Sun - One of the best experts on this subject based on the ideXlab platform.
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orphan nuclear receptor tlx activates wnt beta catenin signalling to stimulate Neural Stem Cell proliferation and self renewal
Nature Cell Biology, 2010Co-Authors: Guoqiang Sun, Chunnian Zhao, Su Yang, Ronald M Evans, Fred H Gage, Yanhong ShiAbstract:The nuclear receptor TLX (also known as NR2E1) is essential for adult Neural Stem Cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse Neural Stem Cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult Neural Stem Cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote Neural Stem Cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased Cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B Neural Stem Cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of Neural Stem Cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in Neural Stem Cell proliferation. Lentiviral transduction of an active beta-catenin increased Cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate Neural Stem Cell proliferation and self-renewal. Moreover, this study suggests that Neural Stem Cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.
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orphan nuclear receptor tlx recruits histone deacetylases to repress transcription and regulate Neural Stem Cell proliferation
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Guoqiang Sun, Ronald M Evans, Yanhong ShiAbstract:TLX is a transcription factor that is essential for Neural Stem Cell proliferation and self-renewal. However, the molecular mechanism of TLX-mediated Neural Stem Cell proliferation and self-renewal is largely unknown. We show here that TLX recruits histone deacetylases (HDACs) to its downstream target genes to repress their transcription, which in turn regulates Neural Stem Cell proliferation. TLX interacts with HDAC3 and HDAC5 in Neural Stem Cells. The HDAC5-interaction domain was mapped to TLX residues 359–385, which contains a conserved nuclear receptor–coregulator interaction motif IXXLL. Both HDAC3 and HDAC5 have been shown to be recruited to the promoters of TLX target genes along with TLX in Neural Stem Cells. Recruitment of HDACs led to transcriptional repression of TLX target genes, the cyclin-dependent kinase inhibitor, p21CIP1/WAF1(p21), and the tumor suppressor gene, pten. Either inhibition of HDAC activity or knockdown of HDAC expression led to marked induction of p21 and pten gene expression and dramatically reduced Neural Stem Cell proliferation, suggesting that the TLX-interacting HDACs play an important role in Neural Stem Cell proliferation. Moreover, expression of a TLX peptide containing the minimal HDAC5 interaction domain disrupted the TLX–HDAC5 interaction. Disruption of this interaction led to significant induction of p21 and pten gene expression and to dramatic inhibition of Neural Stem Cell proliferation. Taken together, these findings demonstrate a mechanism for Neural Stem Cell proliferation through transcriptional repression of p21 and pten gene expression by TLX–HDAC interactions.