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Anti-Olig-2 Antibody

RRID:AB_10141047

Antibody ID

AB_570666

Target Antigen

Olig-2 See NCBI gene human, mouse, rat

Proper Citation

(Millipore Cat# AB9610, RRID:AB_570666)

Clonality

polyclonal antibody

Comments

Entry consolidated by curator with RRID: AB_10141047 on 7/24/17. Vendor recommendations: IC, IH, IH-P, IP, WB.

Host Organism

rabbit

Vendor

Millipore

Myelination of the developing lateral olfactory tract and anterior commissure.

  • Collins LN
  • J. Comp. Neurol.
  • 2018 Aug 1

Literature context:


Abstract:

Both the lateral olfactory tract (LOT) and anterior limb of the anterior commissure (AC) carry olfactory information. The LOT forms the projection from the olfactory bulb to the ipsilateral olfactory cortices, while the AC carries odor information across the midline to the contralateral olfactory cortex and bulb. The LOT and AC differ on a number of dimensions, including early development and functional onset. The present work, examining their myelination in mice, reveals additional important differences. For example, the LOT initiates myelination 3-4 days earlier than the AC, evidenced by both an earlier increase in myelin basic protein staining seen with immunohistochemistry and an earlier appearance of myelinated fibers using electron microscopy. While both exhibit a period of rapid myelination, it occurs 4-5 days earlier in the LOT than the AC. The tracts also respond differently to early sensory restriction. Unilateral naris occlusion from the day after birth to postnatal day 30 had no consistent effects on the AC but resulted in significantly thinner myelin sheaths relative to axon caliber in the LOT. Finally, the two tracts differ structurally (the LOT contains larger, more densely packed axons with significantly thicker myelin sheaths resulting in a conduction velocity that is more than twice as fast as the AC). The findings indicate that these two large, accessible tracts provide an important means for studying brain maturation due to basic differences in both the timing of their maturation and general organization.

Funding information:
  • Medical Research Council - MC_U105178788(United Kingdom)
  • NIDCD NIH HHS - R01 DC000338()
  • NIDCD NIH HHS - R01 DC000407()

Dual Requirement of CHD8 for Chromatin Landscape Establishment and Histone Methyltransferase Recruitment to Promote CNS Myelination and Repair.

  • Zhao C
  • Dev. Cell
  • 2018 Jun 18

Literature context:


Abstract:

Disruptive mutations in chromatin remodeler CHD8 cause autism spectrum disorders, exhibiting widespread white matter abnormalities; however, the underlying mechanisms remain elusive. We show that cell-type specific Chd8 deletion in oligodendrocyte progenitors, but not in neurons, results in myelination defects, revealing a cell-intrinsic dependence on CHD8 for oligodendrocyte lineage development, myelination and post-injury remyelination. CHD8 activates expression of BRG1-associated SWI/SNF complexes that in turn activate CHD7, thus initiating a successive chromatin remodeling cascade that orchestrates oligodendrocyte lineage progression. Genomic occupancy analyses reveal that CHD8 establishes an accessible chromatin landscape, and recruits MLL/KMT2 histone methyltransferase complexes distinctively around proximal promoters to promote oligodendrocyte differentiation. Inhibition of histone demethylase activity partially rescues myelination defects of CHD8-deficient mutants. Our data indicate that CHD8 exhibits a dual function through inducing a cascade of chromatin reprogramming and recruiting H3K4 histone methyltransferases to establish oligodendrocyte identity, suggesting potential strategies of therapeutic intervention for CHD8-associated white matter defects.

Funding information:
  • NIMH NIH HHS - R01 MH087592(United States)

Protease activated receptor 2 controls myelin development, resiliency and repair.

  • Yoon H
  • Glia
  • 2018 Jun 5

Literature context:


Abstract:

Oligodendrocytes are essential regulators of axonal energy homeostasis and electrical conduction and emerging target cells for restoration of neurological function. Here we investigate the role of protease activated receptor 2 (PAR2), a unique protease activated G protein-coupled receptor, in myelin development and repair using the spinal cord as a model. Results demonstrate that genetic deletion of PAR2 accelerates myelin production, including higher proteolipid protein (PLP) levels in the spinal cord at birth and higher levels of myelin basic protein and thickened myelin sheaths in adulthood. Enhancements in spinal cord myelin with PAR2 loss-of-function were accompanied by increased numbers of Olig2- and CC1-positive oligodendrocytes, as well as in levels of cyclic adenosine monophosphate (cAMP), and extracellular signal related kinase 1/2 (ERK1/2) signaling. Parallel promyelinating effects were observed after blocking PAR2 expression in purified oligodendrocyte cultures, whereas inhibiting adenylate cyclase reversed these effects. Conversely, PAR2 activation reduced PLP expression and this effect was prevented by brain derived neurotrophic factor (BDNF), a promyelinating growth factor that signals through cAMP. PAR2 knockout mice also showed improved myelin resiliency after traumatic spinal cord injury and an accelerated pattern of myelin regeneration after focal demyelination. These findings suggest that PAR2 is an important controller of myelin production and regeneration, both in the developing and adult spinal cord.

Characterization of the canine rostral ventricular-subventricular zone: Morphological, immunohistochemical, ultrastructural, and neurosphere assay studies.

  • Fernández-Flores F
  • J. Comp. Neurol.
  • 2018 Mar 1

Literature context:


Abstract:

The mammalian ventricular-subventricular zone (V-SVZ) presents the highest neurogenic potential in the brain of the adult individual. In rodents, it is mainly composed of chains of neuroblasts. In humans, it is organized in layers where neuroblasts do not form chains. The aim of this study is to describe the cytoarchitecture of canine V-SVZ (cV-SVZ), to assess its neurogenic potential, and to compare our results with those previously described in other species. We have studied by histology, immunohistochemistry (IHC), electron microscopy and neurosphere assay the morphology, cytoarchitecture and neurogenic potential of cV-SVZ. Age groups of animals were performed. Histological and ultrastructural studies indicated that the cV-SVZ is organized in layers as in humans, but including migratory chains as in rodents. Neural progenitors were organized in niches in the subependymal area and a decline in their number was observed with age. Adult-young dogs contained migratory cells capable to expand and differentiate in vitro according with previous results obtained in rodents, primates, humans, pigs, and dogs. Some adult animals presented perivascular niches outside the V-SVZ. Our observations evidence a great similarity between canine and human V-SVZ indicating that the dog may be better representative of neurogenic events in humans, compared with rodents. Accordingly with our results, we conclude that dogs are a valuable animal model of adult neurogenesis in comparative and preclinical studies.

Funding information:
  • NIGMS NIH HHS - R01-GM028630(United States)

Efficient Remyelination Requires DNA Methylation.

  • Moyon S
  • eNeuro
  • 2018 Jan 29

Literature context:


Abstract:

Oligodendrocyte progenitor cells (OPCs) are the principal source of new myelin in the central nervous system. A better understanding of how they mature into myelin-forming cells is of high relevance for remyelination. It has recently been demonstrated that during developmental myelination, the DNA methyltransferase 1 (DNMT1), but not DNMT3A, is critical for regulating proliferation and differentiation of OPCs into myelinating oligodendrocytes (OLs). However, it remains to be determined whether DNA methylation is also critical for the differentiation of adult OPCs during remyelination. After lysolecithin-induced demyelination in the ventrolateral spinal cord white matter of adult mice of either sex, we detected increased levels of DNA methylation and higher expression levels of the DNA methyltransferase DNMT3A and lower levels of DNMT1 in differentiating adult OLs. To functionally assess the role of DNMT1 and DNMT3 in adult OPCs, we used mice with inducible and lineage-specific ablation of Dnmt3a and/or Dnmt1 (i.e., Plp-creER(t);Dnmt3a-flox, Plp-creER(t);Dnmt1-flox, Plp-creER(t);Dnmt1-flox;Dnmt3a-flox). Upon lysolecithin injection in the spinal cord of these transgenic mice, we detected defective OPC differentiation and inefficient remyelination in the Dnmt3a null and Dnmt1/Dnmt3a null mice, but not in the Dnmt1 null mice. Taken together with previous results in the developing spinal cord, these data suggest an age-dependent role of distinct DNA methyltransferases in the oligodendrocyte lineage, with a dominant role for DNMT1 in neonatal OPCs and for DNMT3A in adult OPCs.

Funding information:
  • NINDS NIH HHS - R01 NS052738()

Long-lasting masculinizing effects of postnatal androgens on myelin governed by the brain androgen receptor.

  • Abi Ghanem C
  • PLoS Genet.
  • 2017 Nov 21

Literature context:


Abstract:

The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females. Here, we show that these sex differences emerge during the first 10 postnatal days, precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts differentiating. Androgen levels, analyzed by gas chromatography/tandem-mass spectrometry, were higher in males than in females during this period. Treating male pups with flutamide, an androgen receptor (AR) antagonist, or female pups with 5α-dihydrotestosterone (5α-DHT), revealed the importance of postnatal androgens in masculinizing myelin and their persistent effect into adulthood. A key role of the brain AR in establishing the sexual phenotype of myelin was demonstrated by its conditional deletion. Our results uncover a new persistent effect of postnatal AR signaling, with implications for neurodevelopmental disorders and sex differences in multiple sclerosis.

Funding information:
  • NIMH NIH HHS - R01 MH095995(United States)

Myelinogenic Plasticity of Oligodendrocyte Precursor Cells following Spinal Cord Contusion Injury.

  • Assinck P
  • J. Neurosci.
  • 2017 Sep 6

Literature context:


Abstract:

Spontaneous remyelination occurs after spinal cord injury (SCI), but the extent of myelin repair and identity of the cells responsible remain incompletely understood and contentious. We assessed the cellular origin of new myelin by fate mapping platelet-derived growth factor receptor α (PDGFRα), Olig2+, and P0+ cells following contusion SCI in mice. Oligodendrocyte precursor cells (OPCs; PDGFRα+) produced oligodendrocytes responsible for de novo ensheathment of ∼30% of myelinated spinal axons at injury epicenter 3 months after SCI, demonstrating that these resident cells are a major contributor to oligodendrocyte regeneration. OPCs also produced the majority of myelinating Schwann cells in the injured spinal cord; invasion of peripheral myelinating (P0+) Schwann cells made only a limited contribution. These findings reveal that PDGFRα+ cells perform diverse roles in CNS repair, as multipotential progenitors that generate both classes of myelinating cells. This endogenous repair might be exploited as a therapeutic target for CNS trauma and disease.SIGNIFICANCE STATEMENT Spinal cord injury (SCI) leads to profound functional deficits, though substantial numbers of axons often survive. One possible explanation for these deficits is loss of myelin, creating conduction block at the site of injury. SCI leads to oligodendrocyte death and demyelination, and clinical trials have tested glial transplants to promote myelin repair. However, the degree and duration of myelin loss, and the extent and mechanisms of endogenous repair, have been contentious issues. Here, we use genetic fate mapping to demonstrate that spontaneous myelin repair by endogenous oligodendrocyte precursors is much more robust than previously recognized. These findings are relevant to many types of CNS pathology, raising the possibility that CNS precursors could be manipulated to repair myelin in lieu of glial transplantation.

Funding information:
  • NIDDK NIH HHS - DK072473(United States)

Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican.

  • Favuzzi E
  • Neuron
  • 2017 Aug 2

Literature context:


Abstract:

Activity-dependent neuronal plasticity is a fundamental mechanism through which the nervous system adapts to sensory experience. Several lines of evidence suggest that parvalbumin (PV+) interneurons are essential in this process, but the molecular mechanisms underlying the influence of experience on interneuron plasticity remain poorly understood. Perineuronal nets (PNNs) enwrapping PV+ cells are long-standing candidates for playing such a role, yet their precise contribution has remained elusive. We show that the PNN protein Brevican is a critical regulator of interneuron plasticity. We find that Brevican simultaneously controls cellular and synaptic forms of plasticity in PV+ cells by regulating the localization of potassium channels and AMPA receptors, respectively. By modulating Brevican levels, experience introduces precise molecular and cellular modifications in PV+ cells that are required for learning and memory. These findings uncover a molecular program through which a PNN protein facilitates appropriate behavioral responses to experience by dynamically gating PV+ interneuron function.

Cholesterol Modification of Smoothened Is Required for Hedgehog Signaling.

  • Xiao X
  • Mol. Cell
  • 2017 Apr 6

Literature context:


Abstract:

Hedgehog (Hh) has been known as the only cholesterol-modified morphogen playing pivotal roles in development and tumorigenesis. A major unsolved question is how Hh signaling regulates the activity of Smoothened (SMO). Here, we performed an unbiased biochemical screen and identified that SMO was covalently modified by cholesterol on the Asp95 (D95) residue through an ester bond. This modification was inhibited by Patched-1 (Ptch1) but enhanced by Hh. The SMO(D95N) mutation, which could not be cholesterol modified, was refractory to Hh-stimulated ciliary localization and failed to activate downstream signaling. Furthermore, homozygous SmoD99N/D99N (the equivalent residue in mouse) knockin mice were embryonic lethal with severe cardiac defects, phenocopying the Smo-/- mice. Together, the results of our study suggest that Hh signaling transduces to SMO through modulating its cholesterylation and provides a therapeutic opportunity to treat Hh-pathway-related cancers by targeting SMO cholesterylation.

An interaction network of mental disorder proteins in neural stem cells.

  • Moen MJ
  • Transl Psychiatry
  • 2017 Apr 4

Literature context:


Abstract:

Mental disorders (MDs) such as intellectual disability (ID), autism spectrum disorders (ASD) and schizophrenia have a strong genetic component. Recently, many gene mutations associated with ID, ASD or schizophrenia have been identified by high-throughput sequencing. A substantial fraction of these mutations are in genes encoding transcriptional regulators. Transcriptional regulators associated with different MDs but acting in the same gene regulatory network provide information on the molecular relation between MDs. Physical interaction between transcriptional regulators is a strong predictor for their cooperation in gene regulation. Here, we biochemically purified transcriptional regulators from neural stem cells, identified their interaction partners by mass spectrometry and assembled a protein interaction network containing 206 proteins, including 68 proteins mutated in MD patients and 52 proteins significantly lacking coding variation in humans. Our network shows molecular connections between established MD proteins and provides a discovery tool for novel MD genes. Network proteins preferentially co-localize on the genome and cooperate in disease-relevant gene regulation. Our results suggest that the observed transcriptional regulators associated with ID, ASD or schizophrenia are part of a transcriptional network in neural stem cells. We find that more severe mutations in network proteins are associated with MDs that include lower intelligence quotient (IQ), suggesting that the level of disruption of a shared transcriptional network correlates with cognitive dysfunction.

Tridimensional Visualization and Analysis of Early Human Development.

  • Belle M
  • Cell
  • 2017 Mar 23

Literature context:


Abstract:

Generating a precise cellular and molecular cartography of the human embryo is essential to our understanding of the mechanisms of organogenesis in normal and pathological conditions. Here, we have combined whole-mount immunostaining, 3DISCO clearing, and light-sheet imaging to start building a 3D cellular map of the human development during the first trimester of gestation. We provide high-resolution 3D images of the developing peripheral nervous, muscular, vascular, cardiopulmonary, and urogenital systems. We found that the adult-like pattern of skin innervation is established before the end of the first trimester, showing important intra- and inter-individual variations in nerve branches. We also present evidence for a differential vascularization of the male and female genital tracts concomitant with sex determination. This work paves the way for a cellular and molecular reference atlas of human cells, which will be of paramount importance to understanding human development in health and disease. PAPERCLIP.

miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS.

  • Wang H
  • Dev. Cell
  • 2017 Mar 27

Literature context:


Abstract:

A lack of sufficient oligodendrocyte myelination contributes to remyelination failure in demyelinating disorders. miRNAs have been implicated in oligodendrogenesis; however, their functions in myelin regeneration remained elusive. Through developmentally regulated targeted mutagenesis, we demonstrate that miR-219 alleles are critical for CNS myelination and remyelination after injury. Further deletion of miR-338 exacerbates the miR-219 mutant hypomyelination phenotype. Conversely, miR-219 overexpression promotes precocious oligodendrocyte maturation and regeneration processes in transgenic mice. Integrated transcriptome profiling and biotin-affinity miRNA pull-down approaches reveal stage-specific miR-219 targets in oligodendrocytes and further uncover a novel network for miR-219 targeting of differentiation inhibitors including Lingo1 and Etv5. Inhibition of Lingo1 and Etv5 partially rescues differentiation defects of miR-219-deficient oligodendrocyte precursors. Furthermore, miR-219 mimics enhance myelin restoration following lysolecithin-induced demyelination as well as experimental autoimmune encephalomyelitis, principal animal models of multiple sclerosis. Together, our findings identify context-specific miRNA-regulated checkpoints that control myelinogenesis and a therapeutic role for miR-219 in CNS myelin repair.

Funding information:
  • NINDS NIH HHS - R01 NS065808()
  • NINDS NIH HHS - R01 NS072427()
  • NINDS NIH HHS - R01 NS075243()
  • NINDS NIH HHS - R21 NS087474()
  • NINDS NIH HHS - R37 NS096359()

Characterization of the Filum terminale as a neural progenitor cell niche in both rats and humans.

  • Chrenek R
  • J. Comp. Neurol.
  • 2017 Feb 15

Literature context:


Abstract:

Neural stem cells (NSCs) reside in a unique microenvironment within the central nervous system (CNS) called the NSC niche. Although they are relatively rare, niches have been previously characterized in both the brain and spinal cord of adult animals. Recently, another potential NSC niche has been identified in the filum terminale (FT), which is a thin band of tissue at the caudal end of the spinal cord. While previous studies have demonstrated that NSCs can be isolated from the FT, the in vivo architecture of this tissue and its relation to other NSC niches in the CNS has not yet been established. In this article we report a histological analysis of the FT NSC niche in postnatal rats and humans. Immunohistochemical characterization reveals that the FT is mitotically active and its cells express similar markers to those in other CNS niches. In addition, the organization of the FT most closely resembles that of the adult spinal cord niche. J. Comp. Neurol. 525:661-675, 2017. © 2016 Wiley Periodicals, Inc.

Variability in the number of abdominal leucokinergic neurons in adult Drosophila melanogaster.

  • Alvarez-Rivero J
  • J. Comp. Neurol.
  • 2017 Feb 15

Literature context:


Abstract:

Developmental plasticity allows individuals with the same genotype to show different phenotypes in response to environmental changes. An example of this is how neuronal diversity is protected at the expense of neuronal number under sustained undernourishment during the development of the Drosophila optic lobe. In the development of the Drosophila central nervous system, neuroblasts go through two phases of neurogenesis separated by a period of mitotic quiescence. Although during embryonic development much evidence indicates that both cell number and the cell fates generated by each neuroblast are very precisely controlled in a cell autonomous manner, after quiescence extrinsic factors control the reactivation of neuroblast proliferation in a fashion that has not yet been elucidated. Moreover, there is very little information about whether environmental changes affect lineage progression during postembryonic neurogenesis. Using as a model system the pattern of abdominal leucokinergic neurons (ABLKs), we have analyzed how changes in a set of environmental factors affect the number of ABLKs generated during postembryonic neurogenesis. We describe the variability in ABLK number between individuals and between hemiganglia of the same individual and, by genetic analysis, we identify the bithorax-complex genes and the ecdysone hormone as critical factors in these differences. We also explore the possible adaptive roles involved in this process. J. Comp. Neurol. 525:639-660, 2017. © 2016 Wiley Periodicals, Inc.

lncRNA Functional Networks in Oligodendrocytes Reveal Stage-Specific Myelination Control by an lncOL1/Suz12 Complex in the CNS.

  • He D
  • Neuron
  • 2017 Jan 18

Literature context:


Abstract:

Long noncoding RNAs (lncRNAs) are emerging as important regulators of cellular functions, but their roles in oligodendrocyte myelination remain undefined. Through de novo transcriptome reconstruction, we establish dynamic expression profiles of lncRNAs at different stages of oligodendrocyte development and uncover a cohort of stage-specific oligodendrocyte-restricted lncRNAs, including a conserved chromatin-associated lncOL1. Co-expression network analyses further define the association of distinct oligodendrocyte-expressing lncRNA clusters with protein-coding genes and predict lncRNA functions in oligodendrocyte myelination. Overexpression of lncOL1 promotes precocious oligodendrocyte differentiation in the developing brain, whereas genetic inactivation of lncOL1 causes defects in CNS myelination and remyelination following injury. Functional analyses illustrate that lncOL1 interacts with Suz12, a component of polycomb repressive complex 2, to promote oligodendrocyte maturation, in part, through Suz12-mediated repression of a differentiation inhibitory network that maintains the precursor state. Together, our findings reveal a key lncRNA epigenetic circuitry through interaction with chromatin-modifying complexes in control of CNS myelination and myelin repair.

Funding information:
  • NINDS NIH HHS - R01 NS072427()
  • NINDS NIH HHS - R01 NS075243()
  • NINDS NIH HHS - R37 NS096359()

Elucidation of target muscle and detailed development of dorsal motor neurons in chick embryo spinal cord.

  • Kobayashi N
  • J. Comp. Neurol.
  • 2013 Sep 1

Literature context:


Abstract:

The avian cervical spinal cord includes motoneurons (MNs) that send their axons through the dorsal roots. They have been called dorsal motoneurons (dMNs) and assumed to correspond to MNs of the accessory nerve that innervate the cucullaris muscle (SAN-MNs). However, their target muscles have not been elucidated to date. The present study sought to determine the targets and the specific combination of transcription factors expressed by dMNs and SAN-MNs and to describe the detailed development of dMNs. Experiments with tracing techniques confirmed that axons of dMNs innervated the cucullaris muscle. Retrogradely labeled dMNs were distributed in the ventral horn of C3 and more caudal segments. In most cases, some dMNs were also observed in the C2 segment. It was also demonstrated that SAN-MNs existed in the ventral horn of the C1-2 segments and the adjacent caudal hindbrain. Both SAN-MNs and dMNs expressed Isl1 but did not express Isl2, MNR2, or Lhx3. Rather, these MNs expressed Phox2b, a marker for branchial motoneurons (brMNs), although the intensity of expression was weaker. Dorsal MNs and SAN-MNs were derived from the Nkx2.2-positive precursor domain and migrated dorsally. Dorsal MNs remain in the ventral domain of the neural tube, unlike brMNs in the brainstem. These results indicate that dMNs and SAN-MNs belong to a common MN population innervating the cucullaris muscle and also suggest that they are similar to brMNs of the brainstem, although there are differences in Phox2b expression and in the final location of each population. J. Comp. Neurol. 521: 2987-3002, 2013. © 2013 Wiley Periodicals, Inc.

Funding information:
  • Biotechnology and Biological Sciences Research Council - BB/D523186/1(United Kingdom)
  • Wellcome Trust - AG13792(United Kingdom)

Spatiotemporal fate map of neurogenin1 (Neurog1) lineages in the mouse central nervous system.

  • Kim EJ
  • J. Comp. Neurol.
  • 2011 May 1

Literature context:


Abstract:

Neurog1 (Ngn1, Neurod3, neurogenin1) is a basic helix-loop-helix (bHLH) transcription factor essential for neuronal differentiation and subtype specification during embryogenesis. Due to the transient expression of Neurog1 and extensive migration of neuronal precursors, it has been challenging to understand the full complement of Neurog1 lineage cells throughout the central nervous system (CNS). Here we labeled and followed Neurog1 lineages using inducible Cre-flox recombination systems with Neurog1-Cre and Neurog1-CreER(T2) BAC (bacterial artificial chromosome) transgenic mice. Neurog1 lineage cells are restricted to neuronal fates and contribute to diverse but discrete populations in each brain region. In the forebrain, Neurog1 lineages include mitral cells and glutamatergic interneurons in the olfactory bulb, pyramidal and granule neurons in the hippocampus, and pyramidal cells in the cortex. In addition, most of the thalamus, but not the hypothalamus, arises from Neurog1 progenitors. Although Neurog1 lineages are largely restricted to glutamatergic neurons, there are multiple exceptions including Purkinje cells and other GABAergic neurons in the cerebellum. This study provides the first overview of the spatiotemporal fate map of Neurog1 lineages in the CNS.

Funding information:
  • Canadian Institutes of Health Research - 202452(Canada)