The Experts below are selected from a list of 6714 Experts worldwide ranked by ideXlab platform
David H Rowitch - One of the best experts on this subject based on the ideXlab platform.
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olig1 is required for noggin induced neonatal myelin repair
Annals of Neurology, 2017Co-Authors: Jennifer K Sabo, Vivi M Heine, John C Silbereis, Lucas Schirmer, Steven W Levison, David H RowitchAbstract:Objective Neonatal white matter injury (NWMI) is a lesion found in preterm infants that can lead to cerebral palsy. Although antagonists of bone morphogenetic protein (BMP) signaling, such as Noggin, promote oligodendrocyte precursor cell (OPC) production after hypoxic-ischemic (HI) injury, the downstream functional targets are poorly understood. The basic helix-loop-helix protein, oligodendrocyte transcription factor 1 (Olig1), promotes oligodendrocyte (OL) development and is essential during remyelination in adult mice. Here, we investigated whether Olig1 function is required downstream of BMP antagonism for response to injury in the neonatal brain. Methods We used wild-type and Olig1-null mice subjected to neonatal stroke and postnatal neural progenitor cultures, and we analyzed Olig1 expression in human postmortem samples from neonates that suffered HI encephalopathy (HIE). Results Olig1-null neonatal mice showed significant hypomyelination after moderate neonatal stroke. Surprisingly, damaged white matter tracts in Olig1-null mice lacked OLIG2+ OPCs, and instead proliferating neuronal precursors and GABAergic interneurons were present. We demonstrate that Noggin-induced OPC production requires Olig1 function. In postnatal neural progenitors, Noggin governs production of OLs versus interneurons through Olig1-mediated repression of Dlx1/2 transcription factors. Additionally, we observed that Olig1 and the BMP signaling effector, phosphorylated SMADs (Sma- and Mad-related proteins) 1, 5, and 8, were elevated in the subventricular zone of human infants with HIE compared to controls. Interpretation These findings indicate that Olig1 has a critical function in regulation of postnatal neural progenitor cell production in response to Noggin. Ann Neurol 2017;81:560–571
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Lineage-Restricted OLIG2-RTK Signaling Governs the Molecular Subtype of Glioma Stem-like Cells.
Cell reports, 2016Co-Authors: Robert Kupp, David H Rowitch, Lior Shtayer, An-chi Tien, Emily Szeto, Nader Sanai, Shwetal MehtaAbstract:Summary The basic helix-loop-helix (bHLH) transcription factor OLIG2 is a master regulator of oligodendroglial fate decisions and tumorigenic competence of glioma stem-like cells (GSCs). However, the molecular mechanisms underlying dysregulation of OLIG2 function during gliomagenesis remains poorly understood. Here, we show that OLIG2 modulates growth factor signaling in two distinct populations of GSCs, characterized by expression of either the epidermal growth factor receptor (EGFR) or platelet-derived growth factor receptor alpha (PDGFRα). Biochemical analyses of OLIG2 function in normal and malignant neural progenitors reveal a positive feedforward loop between OLIG2 and EGFR to sustain co-expression. Furthermore, loss of OLIG2 function results in mesenchymal transformation in PDGFRα HIGH GSCs, a phenomenon that appears to be circumscribed in EGFR HIGH GSCs. Exploitation of OLIG2′s dual and antithetical, pro-mitotic (EGFR-driven), and lineage-specifying (PDGFRα-driven) functions by glioma cells appears to be critical for sustaining growth factor signaling and GSC molecular subtype.
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An Amino Terminal Phosphorylation Motif Regulates Intranuclear Compartmentalization of OLIG2 in Neural Progenitor Cells
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014Co-Authors: Dimphna H. Meijer, David H Rowitch, John A. Alberta, Michael F Kane, Yu Sun, Tao Liu, Guillaume Adelmant, Robert Kupp, Jarrod A. Marto, Yoshihiro NakataniAbstract:The bHLH transcription factor OLIG2 is expressed in cycling neural progenitor cells but also in terminally differentiated, myelinating oligodendrocytes. Sustained expression of OLIG2 is counterintuitive because all known functions of the protein in expansion of neural progenitors and specification of oligodendrocyte progenitors are completed with the formation of mature white matter. How are the biological functions of OLIG2 suppressed in terminally differentiated oligodendrocytes? In previous studies, we have shown that a triple serine motif in the amino terminus of OLIG2 is phosphorylated in cycling neural progenitors but not in their differentiated progeny. We now show that phosphorylation of the triple serine motif regulates intranuclear compartmentalization of murine OLIG2. Phosphorylated OLIG2 is preferentially localized to a transcriptionally active “open” chromatin compartment together with coregulator proteins essential for regulation of gene expression. Unphosphorylated OLIG2, as seen in mature white matter, is localized mainly within a transcriptionally inactive, chromatin fraction characterized by condensed and inaccessible DNA. Of special note is the observation that the p53 tumor suppressor protein is confined to the open chromatin fraction. Proximity ligation assays show that phosphorylation brings OLIG2 within 30 nm of p53 within the open chromatin compartment. The data thus shed light on previously noted promitogenic functions of phosphorylated OLIG2, which reflect, at least in part, an oppositional relationship with p53 functions.
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separated at birth the functional and molecular divergence of olig1 and OLIG2
Nature Reviews Neuroscience, 2012Co-Authors: Dimphna H. Meijer, Charles D Stiles, Michael F Kane, Shwetal Mehta, Hongye Liu, Emily P Harrington, Christopher M Taylor, David H RowitchAbstract:Despite their structural similarities and seemingly coordinated expression patterns, oligodendrocyte transcription factor 1 (OLIG1) and OLIG2 have largely non-overlapping roles in CNS development, brain diseases and neural repair. Here, the authors review the molecular factors that may account for the divergent functions of these proteins.
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Evidence for motoneuron lineage-specific regulation of OLIG2 in the vertebrate neural tube.
Developmental biology, 2006Co-Authors: Tao Sun, Charles D Stiles, Keith L. Ligon, Dongin Yuk, Brian P. Hafler, Sovann Kaing, Masaaki Kitada, Hans R. Widlund, David H RowitchAbstract:Within the motoneuron precursor (pMN) domain of the developing spinal cord, the bHLH transcription factor, OLIG2, plays critical roles in pattern formation and the generation of motor neuron and oligodendrocyte precursors. How are the multiple functions of OLIG2 regulated? We have isolated a large BAC clone encompassing the human OLIG2 locus that rescues motor neuron and oligodendrocyte development but not normal pattern formation in OLIG2 �/� embryos. Within the BAC clone, we identified a conserved 3.6 kb enhancer sub-region that directs reporter expression specifically in the motor neuron lineage but not oligodendrocyte lineage in vivo. Our findings indicate complex regulation of OLIG2 by stage- and lineage-specific regulatory elements. They further suggest that transcriptional regulation of OLIG2 is involved in segregation of pMN neuroblasts.
Hirohide Takebayashi - One of the best experts on this subject based on the ideXlab platform.
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OLIG2 transcription factor in the developing and injured forebrain; cell lineage and glial development
Molecules and Cells, 2009Co-Authors: Hirohide Takebayashi, Kazuhiro IkenakaAbstract:OLIG2 transcription factor is widely expressed throughout the central nervous system; therefore, it is considered to have multiple functions in the developing, mature and injured brain. In this mini-review, we focus on OLIG2 in the forebrain (telencephalon and diencephalon) and discuss the functional significance of OLIG2 and the differentiation properties of OLIG2-expressing progenitors in the development and injured states. Short- and long-term lineage analysis in the developing forebrain elucidated that not all late OLIG2+ cells are direct cohorts of early cells and that OLIG2 lineage cells differentiate into neurons or glial cells in a region- and stage-dependent manner. OLIG2-deficient mice revealed large elimination of oligodendrocyte precursor cells and a decreased number of astrocyte progenitors in the dorsal cortex, whereas no reduction in the number of GABAergic neurons. In addition to OLIG2 function in the developing cortex, OLIG2 is also reported to be important for glial scar formation after injury. Thus, OLIG2 can be essential for glial differentiation during development and after injury.
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Regional- and temporal-dependent changes in the differentiation of OLIG2 progenitors in the forebrain, and the impact on astrocyte development in the dorsal pallium
Developmental biology, 2008Co-Authors: Katsuhiko Ono, Hirohide Takebayashi, Keisuke Watanabe, Miki Furusho, Kazuyo Ikeda, Takumi Nishizawa, Kazuhiro IkenakaAbstract:OLIG2 is a basic helix-loop-helix transcription factor essential for oligodendrocyte and motoneuron development in the spinal cord. OLIG2-positive (OLIG2+) cells in the ventricular zone of the ventral telencephalon have been shown to differentiate into GABAergic and cholinergic neurons. However, the fate of OLIG2 lineage cells in the postnatal forebrain has not been fully described and OLIG2 may regulate the development of both astrocytes and oligodendrocytes. Here, we examined the fate of embryonic OLIG2+ progenitors using a tamoxifen-inducible Cre/loxP system. Using long-term lineage tracing, OLIG2+ cells in the early fetal stage primarily differentiated into GABAergic neurons in the adult telencephalon, while those in later stages gave rise to macroglial cells, both astrocytes and oligodendrocytes. OLIG2+ progenitors in the diencephalon developed into oligodendrocytes, as observed in the spinal cord, and a fraction developed into glutamatergic neurons. OLIG2 lineage oligodendrocytes tended to form clusters, probably due to local proliferation at the site of terminal differentiation. In spite of the abundance of OLIG2 lineage GABAergic neurons in the normal neocortex, GABAergic neurons seemed to develop at normal density in the OLIG2 deficient mouse. Thus, OLIG2 is dispensable for GABAergic neuron specification. In contrast, at the late fetal stage in the OLIG2 deficient mouse, astrocyte development was retarded in the dorsal neocortex, but not in the basal forebrain. OLIG2 functions, therefore, in gliogenesis in the dorsal pallium. Short-term lineage tracing experiments revealed that the majority of late OLIG2+ cells were not direct descendants of early OLIG2+ progenitors in the fetal forebrain. These observations indicate that embryonic OLIG2+ progenitor cells change their differentiative properties during development, and also that OLIG2 plays a role in astrocyte development in a region-specific manner.
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Genetic fate mapping of OLIG2 progenitors in the injured adult cerebral cortex reveals preferential differentiation into astrocytes
Journal of neuroscience research, 2008Co-Authors: Kouko Tatsumi, Hiroaki Okuda, Hirohide Takebayashi, Takayuki Manabe, Kenji F. Tanaka, Manabu Makinodan, Takahira Yamauchi, Eri Makinodan, Hiroko Matsuyoshi, Kazuhiro IkenakaAbstract:OLIG2 is a basic helix-loop-helix (bHLH) transcription factor essential for development of motoneurons and oligodendrocytes. It is known that OLIG2(+) cells persist in the central nervous system (CNS) from embryonic to adult stages and that the number of OLIG2(+) progenitors increases in the injured adult CNS. Recent studies have demonstrated an inhibitory action of OLIG2 on neurogenesis in adult CNS, but the fate of OLIG2(+) cells in the injured state remains largely unknown. To trace directly the fate of OLIG2 cells in the adult cerebral cortex after injury, we employed the CreER/loxP system to target the OLIG2 locus. In this genetic tracing study, green fluorescent protein (GFP) reporter-positive cells labeled after cryoinjury coexpressed glial fibrillary acidic protein (GFAP), an astrocytic marker. Electron microscopy also showed that GFP(+) cells have the ultrastructural characteristics of astrocytes. Furthermore, GFP(+) cells labeled before injury, most of which had been NG2 cells, also produced bushy astrocytes. Here we show direct evidence that OLIG2(+) cells preferentially differentiate into astrocytes, which strongly express GFAP, in response to injury in the adult cerebral cortex. These results suggest that reactive astrocytes, known to be the main contributors to glial scars, originate, at least in part, from OLIG2(+) cells.
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Expression of the basic helix–loop–factor OLIG2 in the developing retina: OLIG2 as a new marker for retinal progenitors and late-born cells
Gene Expression Patterns, 2006Co-Authors: Koji Shibasaki, Hirohide Takebayashi, Kazuhiro Ikenaka, Liang Feng, Lin GanAbstract:In this study, we examined the spatiotemporal expression patterns of OLIG2, a basic helix-loop-helix transcription factor, in the developing mouse retina. Expression of OLIG2 was initially detected on embryonic day 12.5 (E12.5). The majority of OLIG2-positive cells were identified as retinal progenitor cells throughout embryogenesis. During later embryonic stages, the number of OLIG2-positive retinal progenitor cells increased, and OLIG2-positive cells were confined only to the neuroblast layer (NBL). OLIG2 expression was not observed in the ganglion cell layer (GCL) nor in the inner nuclear layer (INL) that contain the differentiated retinal cell types, indicating that OLIG2 is not expressed in differentiated cells in prenatal retina. In later postnatal stages, OLIG2 expression was retained in mature neurons and glial cells, namely retinal ganglion cells (RGCs), amacrine cells (ACs), horizontal cells, bipolar cells and Muller glial cells. Thus, OLIG2 is an marker both for retinal progenitor cells during embryonic stages, and also for differentiated retinal subpopulations within the GCL and INL during postnatal stages.
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Expression of the basic helix-loop-factor OLIG2 in the developing retina: OLIG2 as a new marker for retinal progenitors and late-born cells.
Gene expression patterns : GEP, 2006Co-Authors: Koji Shibasaki, Hirohide Takebayashi, Kazuhiro Ikenaka, Liang Feng, Lin GanAbstract:In this study, we examined the spatiotemporal expression patterns of OLIG2, a basic helix-loop-helix transcription factor, in the developing mouse retina. Expression of OLIG2 was initially detected on embryonic day 12.5 (E12.5). The majority of OLIG2-positive cells were identified as retinal progenitor cells throughout embryogenesis. During later embryonic stages, the number of OLIG2-positive retinal progenitor cells increased, and OLIG2-positive cells were confined only to the neuroblast layer (NBL). OLIG2 expression was not observed in the ganglion cell layer (GCL) nor in the inner nuclear layer (INL) that contain the differentiated retinal cell types, indicating that OLIG2 is not expressed in differentiated cells in prenatal retina. In later postnatal stages, OLIG2 expression was retained in mature neurons and glial cells, namely retinal ganglion cells (RGCs), amacrine cells (ACs), horizontal cells, bipolar cells and Müller glial cells. Thus, OLIG2 is an marker both for retinal progenitor cells during embryonic stages, and also for differentiated retinal subpopulations within the GCL and INL during postnatal stages.
Kazuhiro Ikenaka - One of the best experts on this subject based on the ideXlab platform.
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OLIG2 transcription factor in the developing and injured forebrain; cell lineage and glial development
Molecules and Cells, 2009Co-Authors: Hirohide Takebayashi, Kazuhiro IkenakaAbstract:OLIG2 transcription factor is widely expressed throughout the central nervous system; therefore, it is considered to have multiple functions in the developing, mature and injured brain. In this mini-review, we focus on OLIG2 in the forebrain (telencephalon and diencephalon) and discuss the functional significance of OLIG2 and the differentiation properties of OLIG2-expressing progenitors in the development and injured states. Short- and long-term lineage analysis in the developing forebrain elucidated that not all late OLIG2+ cells are direct cohorts of early cells and that OLIG2 lineage cells differentiate into neurons or glial cells in a region- and stage-dependent manner. OLIG2-deficient mice revealed large elimination of oligodendrocyte precursor cells and a decreased number of astrocyte progenitors in the dorsal cortex, whereas no reduction in the number of GABAergic neurons. In addition to OLIG2 function in the developing cortex, OLIG2 is also reported to be important for glial scar formation after injury. Thus, OLIG2 can be essential for glial differentiation during development and after injury.
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Regional- and temporal-dependent changes in the differentiation of OLIG2 progenitors in the forebrain, and the impact on astrocyte development in the dorsal pallium
Developmental biology, 2008Co-Authors: Katsuhiko Ono, Hirohide Takebayashi, Keisuke Watanabe, Miki Furusho, Kazuyo Ikeda, Takumi Nishizawa, Kazuhiro IkenakaAbstract:OLIG2 is a basic helix-loop-helix transcription factor essential for oligodendrocyte and motoneuron development in the spinal cord. OLIG2-positive (OLIG2+) cells in the ventricular zone of the ventral telencephalon have been shown to differentiate into GABAergic and cholinergic neurons. However, the fate of OLIG2 lineage cells in the postnatal forebrain has not been fully described and OLIG2 may regulate the development of both astrocytes and oligodendrocytes. Here, we examined the fate of embryonic OLIG2+ progenitors using a tamoxifen-inducible Cre/loxP system. Using long-term lineage tracing, OLIG2+ cells in the early fetal stage primarily differentiated into GABAergic neurons in the adult telencephalon, while those in later stages gave rise to macroglial cells, both astrocytes and oligodendrocytes. OLIG2+ progenitors in the diencephalon developed into oligodendrocytes, as observed in the spinal cord, and a fraction developed into glutamatergic neurons. OLIG2 lineage oligodendrocytes tended to form clusters, probably due to local proliferation at the site of terminal differentiation. In spite of the abundance of OLIG2 lineage GABAergic neurons in the normal neocortex, GABAergic neurons seemed to develop at normal density in the OLIG2 deficient mouse. Thus, OLIG2 is dispensable for GABAergic neuron specification. In contrast, at the late fetal stage in the OLIG2 deficient mouse, astrocyte development was retarded in the dorsal neocortex, but not in the basal forebrain. OLIG2 functions, therefore, in gliogenesis in the dorsal pallium. Short-term lineage tracing experiments revealed that the majority of late OLIG2+ cells were not direct descendants of early OLIG2+ progenitors in the fetal forebrain. These observations indicate that embryonic OLIG2+ progenitor cells change their differentiative properties during development, and also that OLIG2 plays a role in astrocyte development in a region-specific manner.
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Genetic fate mapping of OLIG2 progenitors in the injured adult cerebral cortex reveals preferential differentiation into astrocytes
Journal of neuroscience research, 2008Co-Authors: Kouko Tatsumi, Hiroaki Okuda, Hirohide Takebayashi, Takayuki Manabe, Kenji F. Tanaka, Manabu Makinodan, Takahira Yamauchi, Eri Makinodan, Hiroko Matsuyoshi, Kazuhiro IkenakaAbstract:OLIG2 is a basic helix-loop-helix (bHLH) transcription factor essential for development of motoneurons and oligodendrocytes. It is known that OLIG2(+) cells persist in the central nervous system (CNS) from embryonic to adult stages and that the number of OLIG2(+) progenitors increases in the injured adult CNS. Recent studies have demonstrated an inhibitory action of OLIG2 on neurogenesis in adult CNS, but the fate of OLIG2(+) cells in the injured state remains largely unknown. To trace directly the fate of OLIG2 cells in the adult cerebral cortex after injury, we employed the CreER/loxP system to target the OLIG2 locus. In this genetic tracing study, green fluorescent protein (GFP) reporter-positive cells labeled after cryoinjury coexpressed glial fibrillary acidic protein (GFAP), an astrocytic marker. Electron microscopy also showed that GFP(+) cells have the ultrastructural characteristics of astrocytes. Furthermore, GFP(+) cells labeled before injury, most of which had been NG2 cells, also produced bushy astrocytes. Here we show direct evidence that OLIG2(+) cells preferentially differentiate into astrocytes, which strongly express GFAP, in response to injury in the adult cerebral cortex. These results suggest that reactive astrocytes, known to be the main contributors to glial scars, originate, at least in part, from OLIG2(+) cells.
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Expression of the basic helix–loop–factor OLIG2 in the developing retina: OLIG2 as a new marker for retinal progenitors and late-born cells
Gene Expression Patterns, 2006Co-Authors: Koji Shibasaki, Hirohide Takebayashi, Kazuhiro Ikenaka, Liang Feng, Lin GanAbstract:In this study, we examined the spatiotemporal expression patterns of OLIG2, a basic helix-loop-helix transcription factor, in the developing mouse retina. Expression of OLIG2 was initially detected on embryonic day 12.5 (E12.5). The majority of OLIG2-positive cells were identified as retinal progenitor cells throughout embryogenesis. During later embryonic stages, the number of OLIG2-positive retinal progenitor cells increased, and OLIG2-positive cells were confined only to the neuroblast layer (NBL). OLIG2 expression was not observed in the ganglion cell layer (GCL) nor in the inner nuclear layer (INL) that contain the differentiated retinal cell types, indicating that OLIG2 is not expressed in differentiated cells in prenatal retina. In later postnatal stages, OLIG2 expression was retained in mature neurons and glial cells, namely retinal ganglion cells (RGCs), amacrine cells (ACs), horizontal cells, bipolar cells and Muller glial cells. Thus, OLIG2 is an marker both for retinal progenitor cells during embryonic stages, and also for differentiated retinal subpopulations within the GCL and INL during postnatal stages.
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Expression of the basic helix-loop-factor OLIG2 in the developing retina: OLIG2 as a new marker for retinal progenitors and late-born cells.
Gene expression patterns : GEP, 2006Co-Authors: Koji Shibasaki, Hirohide Takebayashi, Kazuhiro Ikenaka, Liang Feng, Lin GanAbstract:In this study, we examined the spatiotemporal expression patterns of OLIG2, a basic helix-loop-helix transcription factor, in the developing mouse retina. Expression of OLIG2 was initially detected on embryonic day 12.5 (E12.5). The majority of OLIG2-positive cells were identified as retinal progenitor cells throughout embryogenesis. During later embryonic stages, the number of OLIG2-positive retinal progenitor cells increased, and OLIG2-positive cells were confined only to the neuroblast layer (NBL). OLIG2 expression was not observed in the ganglion cell layer (GCL) nor in the inner nuclear layer (INL) that contain the differentiated retinal cell types, indicating that OLIG2 is not expressed in differentiated cells in prenatal retina. In later postnatal stages, OLIG2 expression was retained in mature neurons and glial cells, namely retinal ganglion cells (RGCs), amacrine cells (ACs), horizontal cells, bipolar cells and Müller glial cells. Thus, OLIG2 is an marker both for retinal progenitor cells during embryonic stages, and also for differentiated retinal subpopulations within the GCL and INL during postnatal stages.
Mengsheng Qiu - One of the best experts on this subject based on the ideXlab platform.
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WNT signaling suppresses oligodendrogenesis via Ngn2-dependent direct inhibition of OLIG2 expression.
Molecular brain, 2020Co-Authors: Min Jiang, Mengsheng Qiu, Binghua Xie, Hao Huang, Zhong-min DaiAbstract:OLIG2 transcription factor is essential for the maintenance of neural progenitor cells (NPCs) in the pMN domain and their sequential specification into motor neurons (MNs) and oligodendrocyte precursor cells (OPCs). The expression of OLIG2 rapidly declines in newly generated MNs. However, OLIG2 expression persists in later-born OPCs and antagonizes the expression of MN-related genes. The mechanism underlying the differential expression of OLIG2 in MNs and oligodendrocytes remains unknown. Here, we report that activation of WNT/β-catenin signaling in pMN lineage cells abolished OLIG2 expression coupled with a dramatic increase of Ngn2 expression. Luciferase reporter assay showed that Ngn2 inhibited OLIG2 promoter activity. Overexpression of Ngn2-EnR transcription repressor blocked the expression of OLIG2 in ovo. Our results suggest that down-regulation of WNT-Ngn2 signaling contributes to oligodendrogenesis from the pMN domain and the persistent OLIG2 expression in OPCs.
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Induction of oligodendrocyte differentiation by OLIG2 and Sox10 : Evidence for reciprocal interactions and dosage-dependent mechanisms
Developmental biology, 2006Co-Authors: Zijing Liu, Michael Wegner, Jun Cai, Ben Liu, Xiaozhong Peng, Mengsheng QiuAbstract:Recent studies have suggested that oligodendrocyte development is likely to be under the control of a hierarchy of lineage-specific transcription factors. In the developing mouse spinal cord, expression of OLIG2, Sox10 and Nkx2.2 is sequentially up-regulated in cells of oligodendrocyte lineage. These transcription factors play essential roles in oligodendrocyte specification and differentiation. However, the regulatory relationship and functional interactions among these transcription factors have not been determined. In this study, we systematically investigated the function and hierarchical relationship of OLIG2, Sox10 and Nkx2.2 transcription factors in the control of oligodendrocyte differentiation. It was found that over-expression of OLIG2 is sufficient to induce Sox10, Nkx2.2 and precocious oligodendrocyte differentiation in embryonic chicken spinal cord. Sox10 expression alone is also sufficient to stimulate ectopic oligodendrocyte differentiation and weakly induce Nkx2.2 expression. Although genetic evidence indicated that Sox10 functions downstream of OLIG2, Sox10 activity can modulate OLIG2 expression. In addition, we presented evidence that the control of oligodendrocyte differentiation by OLIG2, Sox10 and Nkx2.2 is a dosage-dependent developmental process and can be affected by both haploinsufficiency and over-dosage.
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generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of nkx6 regulation and shh signaling
Neuron, 2005Co-Authors: Jun Cai, Min Tan, Zijing Liu, Jianshe Zhang, Maike Sander, Mengsheng QiuAbstract:In the developing spinal cord, early progenitor cells of the oligodendrocyte lineage are induced in the motor neuron progenitor (pMN) domain of the ventral neuroepithelium by the ventral midline signal Sonic hedgehog (Shh). The ventral generation of oligodendrocytes requires Nkx6-regulated expression of the bHLH gene OLIG2 in this domain. In the absence of Nkx6 genes or Shh signaling, the initial expression of OLIG2 in the pMN domain is completely abolished. In this study, we provide the in vivo evidence for a late phase of Olig gene expression independent of Nkx6 and Shh gene activities and reveal a brief second wave of oligodendrogenesis in the dorsal spinal cord. In addition, we provide genetic evidence that oligodendrogenesis can occur in the absence of hedgehog receptor Smoothened, which is essential for all hedgehog signaling.
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Dual origin of spinal oligodendrocyte progenitors and evidence for the cooperative role of OLIG2 and Nkx2.2 in the control of oligodendrocyte differentiation.
Development (Cambridge England), 2002Co-Authors: Min Tan, Masato Nakafuku, William D. Richardson, Hirohide Takebayashi, Jun Cai, Mengsheng QiuAbstract:In this study, we have investigated the relationship of OLIG2+ and Nkx2.2+ oligodendrocyte progenitors (OLPs) by comparing the expression of OLIG2 and Nkx2.2 in embryonic chicken and mouse spinal cords before and during the stages of oligodendrogenesis. At the stages of neurogenesis, OLIG2 and Nkx2.2 are expressed in adjacent non-overlapping domains of ventral neuroepithelium. During oligodendrogenesis stages, these two domains generate distinct populations of OLPs. From the OLIG2+ motoneuron precursor domain (pMN) arise the OLIG2+/Pdgfra+ OLPs, whereas the Nkx2.2+ p3 domain give rise to Nkx2.2+ OLPs. Despite their distinct origins, both populations of OLPs eventually appear to co-express OLIG2 and Nkx2.2 in the same cells. However, there is a species difference in the timing of acquiring Nkx2.2 expression by the OLIG2+/Pdgfra+ OLPs. The co-expression of Nkx2.2 and OLIG2 in OLPs is tightly associated with myelin gene expression in the normal and PDGFA–/– embryos, suggesting a cooperative role of these transcription factors in the control of oligodendrocyte differentiation. In support of this suggestion, inhibition of expression of these two transcription factors in culture by antisense oligonucleotides has an additive inhibitory effect on OLP differentiation and proteolipid protein (PLP) gene expression.
Seung U Kim - One of the best experts on this subject based on the ideXlab platform.
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differential and cooperative actions of olig1 and OLIG2 transcription factors on immature proliferating cells after contusive spinal cord injury
Glia, 2011Co-Authors: Hyuk M Kim, Dong H Hwang, Jun Young Choi, Chang Hwan Park, Haeyoung Suhkim, Seung U Kim, Byung Gon KimAbstract:Spontaneous remyelination after spinal cord injury (SCI) is limited probably due to inadequate signaling to generate sufficient OLs from progenitor cells. The present study tested a hypothesis that introduction of olig genes, critical regulators of OL development, into immature proliferating cells could increase oligodendrogenesis after contusive SCI in adult rats. Recombinant retroviruses encoding Olig1 and OLIG2 transcription factors, separately or in combination, with green fluorescent protein (GFP) were injected into the injured spinal cord. Unexpectedly, introduction of OLIG2-GFP retroviruses led to a marked hyperplasia of GFP+ cells at 1 week, and soft agar colony forming assay of isolated GFP+ cells confirmed OLIG2-induced tumorous transformation. In contrast, Olig1 did not alter the number of GFP+ cells. Simultaneous expression of Olig1 and OLIG2 (Olig1/2) led to a marked increase in the number of GFP+ cells without tumor formation. The proportion of GFP+ cells with OL progenitor markers was increased by Olig1/2. Moreover, Olig1/2 robustly increased the proportion of mature OLs and expression of myelin related proteins, while Olig1 alone exhibited only modest effects. Olig1/2 upregulated Sox10, which drives terminal OL differentiation, implicating Sox 10 as a mediator of Olig1/2 effects on the maturation. Finally, injection of Olig1/2 retroviruses significantly improved a quality of hindpaws locomotion and increased the total number of OLs after SCI. Activation of both Olig1 and OLIG2 may be beneficial by both increasing the progenitor cell proliferation and enhancing OL differentiation in the injured spinal cord. © 2011 Wiley-Liss, Inc.
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transplantation of human neural stem cells transduced with OLIG2 transcription factor improves locomotor recovery and enhances myelination in the white matter of rat spinal cord following contusive injury
BMC Neuroscience, 2009Co-Authors: Dong H Hwang, Haeyoung Suhkim, Seung U Kim, Byung Gon Kim, Eun Joo Kim, Seung Ihm Lee, In S Joo, Seonghyang SohnAbstract:Contusive spinal cord injury is complicated by a delayed loss of oligodendrocytes, resulting in chronic progressive demyelination. Therefore, transplantation strategies to provide oligodendrocyte lineage cells and to enhance the extent of myelination appear to be justified for spinal cord repair. The present study investigated whether transplantation of human neural stem cells (NSCs) genetically modified to express OLIG2 transcription factor, an essential regulator of oligodendrocyte development, can improve locomotor recovery and enhance myelination in a rat contusive spinal cord injury model. HB1.F3 (F3) immortalized human NSC line was transduced with a retroviral vector encoding OLIG2, an essential regulator of oligodendrocyte development. Overexpression of OLIG2 in human NSCs (F3.OLIG2) induced activation of NKX2.2 and directed differentiation of NSCs into oligodendrocyte lineage cells in vitro. Introduction of OLIG2 conferred higher proliferative activity, and a much larger number of F3.OLIG2 NSCs were detected by 7 weeks after transplantation into contused spinal cord than that of parental F3 NSCs. F3.OLIG2 NSCs exhibited frequent migration towards the white matter, whereas F3 NSCs were mostly confined to the gray matter or around the lesion cavities. Most of F3.OLIG2 NSCs occupying the spared white matter differentiated into mature oligodendrocytes. Transplantation of F3.OLIG2 NSCs increased the volume of spared white matter and reduced the cavity volume. Moreover, F3.OLIG2 grafts significantly increased the thickness of myelin sheath around the axons in the spared white matter. Finally, animals with F3.OLIG2 grafts showed an improvement in the quality of hindlimbs locomotion. Transplantation of NSCs genetically modified to differentiate into an oligodendrocytic lineage may be an effective strategy to improve functional outcomes following spinal cord trauma. The present study suggests that molecular factors governing cell fate decisions can be manipulated to enhance reparative potential of the cell-based therapy.
