The bHLH Transcription Factors OLIG2 and OLIG1 Couple Neuronal and Glial Subtype Specification

Zhou, Qiao; Anderson, David J.

doi:10.1016/s0092-8674(02)00677-3

Cited by 1,059Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationCongenital heart defects research

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The bHLH Transcription Factors OLIG2 and OLIG1 Couple Neuronal and Glial Subtype Specification

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Zhou, Qiao, Anderson, David J.·2002·Cell

DOI 10.1016/s0092-8674(02)00677-3

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Abstract

OLIG1 and OLIG2 are basic-helix-loop-helix (bHLH) transcription factors expressed in the pMN domain of the spinal cord, which sequentially generates motoneurons and oligodendrocytes. In Olig1/2 double-mutant mice, motoneurons are largely eliminated, and oligodendrocyte differentiation is abolished. Lineage tracing data suggest that Olig1(-/-)2(-/-) pMN progenitors instead generate V2 interneurons and then astrocytes. This apparent conversion likely reflects independent roles for OLIG1/2 in specifying motoneuron and oligodendrocyte fates. Olig genes therefore couple neuronal and glial subtype specification, unlike proneural bHLH factors that control the neuron versus glia decision. Our results suggest that in the spinal cord, Olig and proneural genes comprise a combinatorial code for the specification of neurons, astrocytes, and oligodendrocytes, the three fundamental cell types of the central nervous system.

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Cell type-specific transcription factor expression is important for cell fate determination and cell differentiation.
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From An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex (2014) · cites this paper as Zhou and Anderson, 2002

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“, 1999), and loss of motor neurons in Olig1/2 knockout mice results in a dramatic increase of Chx10 V2a interneurons (Zhou and Anderson, 2002).”
Background
Timing Is Everything: Making Neurons versus Glia in the Developing Cortex
Miller, F. D., & Gauthier, A. S. (2007) · Neuron · doi:10.1016/j.neuron.2007.04.019 · Cited by 588
Identification of intrinsic determinants of midbrain dopamine neurons
Andersson, E., Tryggvason, U., Deng, Q., Friling, S., Alekseenko, Z., Robert, B., Perlmann, T., & Ericson, J. (2006) · Cell · doi:10.1016/j.cell.2005.10.037 · Cited by 587
PDGFRα-Positive B Cells Are Neural Stem Cells in the Adult SVZ that Form Glioma-like Growths in Response to Increased PDGF Signaling
Jackson, E., García-Verdugo, J., Gil-Perotín, S., Roy, M., Quiñones-Hinojosa, A., Vandenberg, S., & Álvarez-Buylla, A. (2006) · Neuron · doi:10.1016/j.neuron.2006.06.012 · Cited by 587
SOX10 maintains multipotency and inhibits neuronal differentiation of neural crest stem cells.
Kim, J., Lo, L., Dormand, E., & Anderson, D. J. (2003) · Neuron · doi:10.1016/s0896-6273(03)00163-6 · Cited by 584
Self-citation
Dicer1 and miR-219 Are Required for Normal Oligodendrocyte Differentiation and Myelination
Dugas, J. C., Cuellar, T. L., Scholze, A., Ason, B., Ibrahim, A., Emery, B., Zamanian, J. L., Foo, L. C., McManus, M. T., & Barres, B. A. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.027 · Cited by 577
Myelin gene regulatory factor is a critical transcriptional regulator required for CNS myelination
Emery, B., Agalliu, D., Cahoy, J. D., Watkins, T. A., Dugas, J. C., Mulinyawe, S. B., Ibrahim, A., Ligon, K. L., Rowitch, D. H., & Barres, B. A. (2009) · Cell · doi:10.1016/j.cell.2009.04.031 · Cited by 559
“Among these, Olig2 is the only gene necessary for the OL lineage specification, with Olig2 / mice showing a loss of PDGFRa-positive OPCs within most of the CNS (Lu et al., 2002; Zhou and Anderson, 2002).”
Background
HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the β-catenin–TCF interaction
Ye, F., Chen, Y., Hoang, T., Montgomery, R. L., Zhao, X.-H., Bu, H., Hu, T., Taketo, M. M., van Es, J. H., Clevers, H., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2333 · Cited by 559
“7).”
Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolution
Trevino, A. E., Müller, F., Andersen, J., Sundaram, L., Kathiria, A., Shcherbina, A., Farh, K., Chang, H. Y., Pașca, A. M., Kundaje, A., et al. (2021) · Cell · doi:10.1016/j.cell.2021.07.039 · Cited by 478
Oligodendrocyte Development and PlasticityPreprint
Bergles, D. E., & Richardson, W. D. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020453 · Cited by 604
Olig2-Regulated Lineage-Restricted Pathway Controls Replication Competence in Neural Stem Cells and Malignant Glioma
Ligon, K. L., Huillard, E., Mehta, S. V., Kesari, S., Liu, H., Alberta, J. A., Bachoo, R. M., Kane, M., Louis, D. N., DePinho, R. A., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.009 · Cited by 524
Self-citation
Math1 expression redefines the rhombic lip derivatives and reveals novel lineages within the brainstem and cerebellum.
Wang, V. Y., Rose, M. F., & Zoghbi, H. (2005) · Neuron · doi:10.1016/j.neuron.2005.08.024 · Cited by 524
“(Bermingham et al., 2001; Zhou and Anderson, 2002).”
The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord
Deneen, B., Ho, R., Lukaszewicz, A., Hochstim, C. J., Gronostajski, R. M., & Anderson, D. J. (2006) · Neuron · doi:10.1016/j.neuron.2006.11.019 · Cited by 514
“…we compared the gene expression profiles of Olig2 + progenitors isolated at different times spanning this developmental transition (Lu et al., 2002; Zhou and Anderson, 2002; Mukouyama et al., 2006 ). cRNA probes were generated from total RNA isolated from these different purified progenitor…”
Self-citation
Oscillatory Control of Factors Determining Multipotency and Fate in Mouse Neural Progenitors
Imayoshi, I., Isomura, A., Harima, Y., Kawaguchi, K., Kori, H., Miyachi, H., Fujiwara, T., Ishidate, F., & Kageyama, R. (2013) · Science · doi:10.1126/science.1242366 · Cited by 509
“The bHLH gene Olig2 regulates oligodendrocyte specification, while the bHLH genes Hes1 and Hes5 maintain NPCs by repressing proneural gene expression (8-12).”
Background
Regional Astrocyte Allocation Regulates CNS Synaptogenesis and Repair
Tsai, H., Li, H., Fuentealba, L. C., Molofsky, A. V., Taveira‐Marques, R., Zhuang, H., Tenney, A., Murnen, A. T., Fancy, S. P. J., Merkle, F. T., et al. (2012) · Science · doi:10.1126/science.1222381 · Cited by 555
The basic helix-loop-helix factor olig2 is essential for the development of motoneuron and oligodendrocyte lineages.
Takebayashi, H., Nabeshima, Y., Yoshida, S., Chisaka, O., Ikenaka, K., & Nabeshima, Y. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00926-0 · Cited by 500
Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior.
Hendricks, T. J., Fyodorov, D., Wegman, L. J., Lelutiu, N. B., Pehek, E. A., Yamamoto, B., Silver, J., Weeber, E., Sweatt, J., & Deneris, E. S. (2003) · Neuron · doi:10.1016/s0896-6273(02)01167-4 · Cited by 486
Gene Regulatory Logic for Reading the Sonic Hedgehog Signaling Gradient in the Vertebrate Neural Tube
Balaskas, N., Ribeiro, A., Panovska‐Griffiths, J., Dessaud, É., Sasai, N., Page, K. M., Briscoe, J., & Ribes, V. (2012) · Cell · doi:10.1016/j.cell.2011.10.047 · Cited by 474
“Mouse Lines Mice containing mutant alleles for Pax6 (Small Eye allele), Olig2, and Gli3 (Xt allele) have been described previously (Ericson et al., 1997; Hui and Joyner, 1993; Zhou and Anderson, 2002).”
Background
The Oligodendroglial Lineage Marker OLIG2 Is Universally Expressed in Diffuse Gliomas
Ligon, K., Alberta, J., Kho, A., Weiss, J., Kwaan, M. R., Nutt, C., Louis, D., Stiles, C., & Rowitch, D. (2004) · Journal of Neuropathology and Experimental Neurology · doi:10.1093/jnen/63.5.499 · Cited by 467
Glial specification in the vertebrate neural tube
Rowitch, D. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1389 · Cited by 432
“Functional analysis in mice has shown that Olig1 and Olig2 are required for establishment of the pMN domai”
Background
Overcoming therapeutic resistance in glioblastoma: the way forward
Osuka, S., & Meir, E. G. V. (2017) · Journal of Clinical Investigation · doi:10.1172/jci89587 · Cited by 526
Regulation of oligodendrocyte development in the vertebrate CNS
Miller, R. H. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00058-8 · Cited by 426
“Oligodendrocyte precursors arise during later development from the motor neuron pool that is characterized by expression of the transcription factor Olig2 (Zhou et al., 2001; Zhou and Anderson, 2002).”
BackgroundInfluential
bHLH Transcription Factor Olig1 Is Required to Repair Demyelinated Lesions in the CNS
Arnett, H. A., Fancy, S. P. J., Alberta, J. A., Zhao, C., Plant, S. R., Kaing, S., Raine, C. S., Rowitch, D. H., Franklin, R. J. M., & Stiles, C. D. (2004) · Science · doi:10.1126/science.1103709 · Cited by 416
Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and Their Differentiated Derivatives
Nazor, K. L., Altun, G., Lynch, C., Tran, H. T. T., Harness, J. V., Slavin, I., Garitaonandia, I., Müller, F.-J., Wang, Y.-C., Boscolo, F. S., et al. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.02.013 · Cited by 411
“…of several genes known to regulate oligodendrocyte differentiation including SKI, QKI, and OLIG2 (Aberg et al., 2006; Atanasoski et al., 2004; Zhou and Anderson, 2002) and the myelin proteins PLP1 and PMP22 (Figure 3D) was observed and reflected in the GREAT enrichments for myelination and…”
Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolutionPreprint
Trevino, A. E., Müller, F., Andersen, J., Sundaram, L., Kathiria, A. S., Shcherbina, A., Farh, K., Chang, H. Y., Pașca, A. M., Kundaje, A., et al. (2020) · bioRxiv · doi:10.1101/2020.12.29.424636 · Cited by 407
“The similarity of annotated motifs for these factors is consistent with the hypothesis that they can compete for similar binding sites to drive multiple distinct cell fates, as has been previously suggested (Imayoshi et al., 2013; Zhou and Anderson, 2002).”
Background
Mash1 specifies neurons and oligodendrocytes in the postnatal brain
Parras, C., Galli, R., Britz, O., Soares, S., Galichet, C., Battiste, J., Johnson, J. E., Nakafuku, M., Vescovi, A., & Guillemot, F. (2004) · EMBO Journal · doi:10.1038/sj.emboj.7600447 · Cited by 404
“…for the generation of GABAergic interneurons and oligodendrocytes The idea that generation of oligodendrocytes and motor neurons is coupled in the spinal cord has recently received strong support from the analysis of mouse mutants (Kessaris et al, 2001; Lu et al, 2002; Zhou and Anderson, 2002).”
BackgroundInfluential
Expression pattern of the transcription factor Olig2 in response to brain injuries: implications for neuronal repair.
Buffo, A., Vosko, M., Ertürk, D., Hamann, G., Jucker, M., Rowitch, D., & Götz, M. (2005) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0506535102 · Cited by 402
Physiologically Distinct Temporal Cohorts of Cortical Interneurons Arise from Telencephalic Olig2 -Expressing Precursors
Miyoshi, G., Butt, S. J. B., Takebayashi, H., & Fishell, G. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1807-07.2007 · Cited by 400
“Here, we study the distinct cohorts of cells arising from progenitors expressing high levels of the basic helix-loop-helix (bHLH) gene Olig2 (Lu et al., 2002; Zhou and Anderson, 2002; Lee et al., 2005).”
Background
Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells
Lim, D. A., Huang, Y.-C., Swigut, T., Mirick, A. L., García‐Verdugo, J. M., Wysocka, J., Ernst, P., & Álvarez-Buylla, A. (2009) · Nature · doi:10.1038/nature07726 · Cited by 390
Oligodendrocyte wars
Richardson, W. D., Kessaris, N., & Pringle, N. (2006) · Nature reviews. Neuroscience · doi:10.1038/nrn1826 · Cited by 385
Radial glia diversity: A matter of cell fate
Kriegstein, A., & Götz, M. (2003) · Glia · doi:10.1002/glia.10250 · Cited by 376
Olig2 Targets Chromatin Remodelers to Enhancers to Initiate Oligodendrocyte Differentiation
Yu, Y., Chen, Y., Kim, B., Wang, H., Zhao, C., He, X., Liu, L., Liu, W., Wu, L. M. N., Mao, M., et al. (2013) · Cell · doi:10.1016/j.cell.2012.12.006 · Cited by 375
Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned
Gudi, V., Gingele, S., Skripuletz, T., & Stangel, M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00073 · Cited by 375
“The basic helix-loop-helix (bHLH) transcription factors Olig1 and Olig2 have been revealed to play a key role in regulating oligodendrocyte development (Zhou et al., 2000; Lu et al., 2001; Zhou and Anderson, 2002; Ligon et al., 2006).”
Background
Molecular mechanisms controlling cortical gliogenesis.
Sauvageot, C., & Stiles, C. (2002) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(02)00322-7 · Cited by 373
Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain
Petryniak, M. A., Potter, G. B., Rowitch, D. H., & Rubenstein, J. L. R. (2007) · Neuron · doi:10.1016/j.neuron.2007.06.036 · Cited by 371
A novel m6A reader Prrc2a controls oligodendroglial specification and myelination
Wu, R., Li, A., Sun, B., Sun, J.-G., Zhang, J., Zhang, T., Chen, Y., Xiao, Y., Gao, Y., Zhang, Q., et al. (2019) · Cell Research · doi:10.1038/s41422-018-0113-8 · Cited by 366
“Previous studies have shown that Olig2 functions as an oligodendroglial lineage determination factor by controlling OPC specification, differentiation, and myelination.(40,41) Therefore, we argue that Olig2 might act as an important target of Prrc2a in regulating oligodendroglial specification.”
Background
A Requirement for Retinoic Acid-Mediated Transcriptional Activation in Ventral Neural Patterning and Motor Neuron Specification
Novitch, B. G., Wichterle, H., Jessell, T. M., & Sockanathan, S. (2003) · Neuron · doi:10.1016/j.neuron.2003.08.006 · Cited by 350
“…that define successive steps in to activate the expression of transcription factors thatMN differentiation (Mizuguchi et al., 2001; Novitch et al., direct later steps in MN differentiation (Figure 6K).2001; Lu et al., 2002; Takebayashi et al., 2002; Zhou and Anderson, 2002; William et al., 2003).”
Background
Interactions between ID and OLIG proteins mediate the inhibitory effects of BMP4 on oligodendroglial differentiation
Samanta, J., & Kessler, J. A. (2004) · Development · doi:10.1242/dev.01273 · Cited by 361
Glioma Stem Cells: A Midterm Exam
Stiles, C. D., & Rowitch, D. H. (2008) · Neuron · doi:10.1016/j.neuron.2008.05.031 · Cited by 336
Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development
Fuccillo, M. V., Joyner, A. L., & Fishell, G. (2006) · Nature reviews. Neuroscience · doi:10.1038/nrn1990 · Cited by 425
The oligodendrocyte-specific G protein–coupled receptor GPR17 is a cell-intrinsic timer of myelination
Chen, Y., Wu, H., Wang, S., Koito, H., Li, J., Ye, F., Hoang, J., Escobar, S. S., Gow, A., Arnett, H. A., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2410 · Cited by 346
Multiple Dorsoventral Origins of Oligodendrocyte Generation in the Spinal Cord and Hindbrain
Vallstedt, A., Klos, J. M., & Ericson, J. (2005) · Neuron · doi:10.1016/j.neuron.2004.12.026 · Cited by 359
Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling.
Cai, J., Qi, Y., Hu, X.-M., Tan, M., Liu, Z., Zhang, J.-S., Li, Q., Sander, M., & Qiu, M.-S. (2005) · Neuron · doi:10.1016/j.neuron.2004.12.028 · Cited by 345
“of Nkx6 Regulation and Shh Signaling type followed by either astrogliogenesis or oligodendrogenesis (Jessell, 2000; Zhou and Anderson, 2002).”
BackgroundMethodInfluential
The Molecular and Genetic Basis of Neurological Tumours
Zhu, Y. S., & Parada, L. F. (2002) · Nature reviews. Cancer · doi:10.1038/nrc866 · Cited by 325
Activation of the subventricular zone in multiple sclerosis: Evidence for early glial progenitors
Nait‐Oumesmar, B., Picard-Riéra, N., Kerninon, C., Decker, L., Seilhean, D., Höglinger, G. U., Hirsch, É. C., Reynolds, R., & Evercooren, A. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606835104 · Cited by 332
Identification of positionally distinct astrocyte subtypes whose identities are specified by a homeodomain code
Hochstim, C., Deneen, B., Lukaszewicz, A., Zhou, Q., & Anderson, D. J. (2008) · Cell · doi:10.1016/j.cell.2008.02.046 · Cited by 331
“In the absence of Olig2, presumptive oligodendrocyte precursors are converted to GFAP+ WMAs (A, B), as demonstrated previously (Zhou and Anderson, 2002).”
InfluentialSelf-citation
Deregulation of dorsoventral patterning by FGF confers trilineage differentiation capacity on CNS stem cells in vitro.
Gabay, L., Lowell, S., Lee, R.-B. L., & Anderson, D. J. (2003) · Neuron · doi:10.1016/s0896-6273(03)00637-8 · Cited by 326
Self-citation
Myelin Regeneration: A Recapitulation of Development?
Fancy, S. P. J., Chan, J. R., Baranzini, S. E., Franklin, R. J. M., & Rowitch, D. H. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113629 · Cited by 339
Functional Genomic Analysis of Oligodendrocyte Differentiation
Dugas, J. C., Tai, Y. C., Speed, T. P., Ngai, J., & Barres, B. A. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2572-06.2006 · Cited by 324
“These include SOX10, OLIG1, and OLIG2, and homeodomain proteins of the Nkx family (Wegner, 2001; Stolt et al., 2002; Zhou and Anderson, 2002; Masahira et al., 2006; Nakamura et al., 2006; Wu et al., 2006).”
Background
Oligodendrocyte development and the onset of myelination in the human fetal brain
Jakovcevski, I. (2009) · Frontiers in Neuroanatomy · doi:10.3389/neuro.05.005.2009 · Cited by 323
“Olig genes belong to a bHLH group of transcription factors that are necessary and suffi cient for generation of oligodendrocytes and for myelination in mice (Lu et al., 2000, 2002; Takebayashi et al., 2002; Tekki-Kessaris et al., 2001; Zhou and Anderson, 2002; Zhou et al., 2000; 2001).”
Background
Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma
Monje, M., Mitra, S., Freret, M., Raveh, T., Kim, J., Masek, M., Attema, J., Li, G., Haddix, T., Edwards, M. S., et al. (2011) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1101657108 · Cited by 316
olig2 is required for zebrafish primary motor neuron and oligodendrocyte development.
Park, H.-C., Mehta, A., Richardson, J., & Appel, B. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0738 · Cited by 316
“These data are consistent with recent reports describing mouse embryos lacking Olig1 and Olig2 functions resulting from targeted mutagenesis (Lu et al., 2002; Zhou and Anderson, 2002).”
Result
Chapter Six Hox Networks and the Origins of Motor Neuron Diversity
Dasen, J. S., & Jessell, T. M. (2009) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(09)88006-x · Cited by 326
“2 (Novitch et al., 2001; Vallstedt et al., 2001; Zhou and Anderson, 2002).”
Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice
Yamanaka, K., Boillee, S., Roberts, E. A., Garcia, M. L., McAlonis-Downes, M., Mikse, O. R., Cleveland, D. W., & Goldstein, L. S. B. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802556105 · Cited by 309
“mice (a gift from D Anderson, California Institute of Technology) (18).”
BackgroundMethodInfluential
Spatial and temporal specification of neural fates by transcription factor codes
Guillemot, F. (2007) · Development · doi:10.1242/dev.006379 · Cited by 308
“2 in the chick spinal cord is sufficient to induce oligodendrocyte precursors at ectopic locations (Lu et al., 2002; Zhou and Anderson, 2002; Zhou et al., 2001).”
Background
Motor neurons and the generation of spinal motor neuron diversity
Stifani, N. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00293 · Cited by 389
“In turn, GLI proteins promote or repress in a concentration dependent manner homeodomain transcription factors that can be sorted into two classes: (i) ClassI; paired box 3/6/7 (PAX3/6/7), developing brain homeobox 1 and 2 (DBX1/2), and Iroquois related homeobox 3 (IRX3) are repressed by GliA and thus expressed dorsal…”
BackgroundInfluential
Synchronization of Neurogenesis and Motor Neuron Specification by Direct Coupling of bHLH and Homeodomain Transcription Factors
Lee, S., & Pfaff, S. L. (2003) · Neuron · doi:10.1016/s0896-6273(03)00296-4 · Cited by 288
Delta-Notch signaling controls the generation of neurons/glia from neural stem cells in a stepwise process
Grandbarbe, L., Bouissac, J., Rand, M., de Angelis, M. H., Artavanis‐Tsakonas, S., & Mohier, E. (2003) · Development · doi:10.1242/dev.00374 · Cited by 286
“We therefore conclude that the segregation between oligodendrocyte and astrocyte lineages is independent of Notch signaling and might derive from another mechanism, involving for example the transcription factors OLIG1 and OLIG2 (Zhou and Anderson, 2002).”
Background
Neural cell fate analysis in zebrafish using olig2 BAC transgenics.
Shin, J., Park, H.-C., Topczewska, J. M., Mawdsley, D., & Appel, B. (2003) · Methods in Cell Science · doi:10.1023/b:mics.0000006847.09037.3a · Cited by 295
Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6.
Hack, M., Sugimori, M., Lundberg, C., Nakafuku, M., & Götz, M. (2004) · Molecular and cellular neurosciences · doi:10.1016/j.mcn.2003.12.012 · Cited by 294
Neural Subtype Specification from Human Pluripotent Stem Cells
Tao, Y., & Zhang, S.-C. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.10.015 · Cited by 287
“The best-characterized origin is at the ventral part of telencephalon and spinal cord where the oligodendrocyte progenitor cells (OPCs) are specified from NE in response to SHH signal by expressing the Olig1/2 gene (Lu et al., 2002; Zhou and Anderson, 2002).”
Background
bHLH Factors in Self-Renewal, Multipotency, and Fate Choice of Neural Progenitor Cells
Imayoshi, I., & Kageyama, R. (2014) · Neuron · doi:10.1016/j.neuron.2014.03.018 · Cited by 279
“Olig2 single and Olig1/2 double knockout mice lack oligodendrocyte lineage cells (Lu et al., 2002; Zhou and Anderson, 2002; Takebayashi et al., 2002), whereas forced expression of Olig1/2 in NPCs is sufficient to induce the specification of oligodendrocyte precursor cells (OPCs) (Zhou et al., 2001;…”
Transcriptional and Epigenetic Regulation of Oligodendrocyte Development and Myelination in the Central Nervous SystemPreprint
Emery, B., & Lu, Q. R. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020461 · Cited by 307
MYRF is a membrane-associated transcription factor that autoproteolytically cleaves to directly activate myelin genes
Bujalka, H., Koenning, M., Jackson, S., Perreau, V. M., Pope, B., Hay, C. M., Mitew, S., Hill, A. F., Lu, Q. R., Wegner, M., et al. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001625 · Cited by 271
A subset of oligodendrocytes generated from radial glia in the dorsal spinal cord
Fogarty, M., Richardson, W., & Kessaris, N. (2005) · Development · doi:10.1242/dev.01777 · Cited by 270
“Shh induces expression of the basic helix-loop-helix transcription factor Olig2, which is required for the generation of both MNs and OLPs (Lu et al., 2002; Zhou and Anderson, 2002; Takebayashi et al., 2002).”
Background
Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging
Stein, L. R., & Imai, S. (2014) · The EMBO Journal · doi:10.1002/embj.201386917 · Cited by 265
“One main regulator of these factors is the basic helix-loop-helix transcription factor Olig2 (Takebayashi et al, 2002; Zhou & Anderson, 2002; Ligon et al, 2007; Wegner, 2008).”
Background
Extreme Makeover: Converting One Cell into Another
Zhou, Q., & Melton, D. A. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.09.015 · Cited by 255
“For example, there is a large body of knowledge about the lineages of neurons and their associated glial cells, and the genetic codes that govern their generation during embryogenesis are being elucidated (Hochstim et al., 2008; Jessell, 2000; Zhou and Anderson, 2002).”
BackgroundSelf-citation
Mechanisms regulating the development of oligodendrocytes and central nervous system myelin
Mitew, S., Hay, C. M., Peckham, H., Xiao, J., Koenning, M., & Emery, B. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.11.029 · Cited by 268
“The importance of OLIG2 function in the specification of the oligodendrocyte lineage is well-established; Olig2 gene knockouts fail to produce OPCs within most regions of the CNS (Lu et al., 2002; Zhou and Anderson, 2002; Ligon et al., 2006), and inducible expression of Olig2 in Nestin-positive progenitor cells result…”
BackgroundInfluential
Glial Cells as Progenitors and Stem Cells: New Roles in the Healthy and Diseased Brain
Dimou, L., & Götz, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00036.2013 · Cited by 285
Olig1 and Olig2 triplication causes developmental brain defects in down syndrome.
Chakrabarti, L., Best, T. K., Cramer, N. P., Carney, R. S. E., Isaac, J. T. R., Galdzicki, Z., & Haydar, T. F. (2010) · Nature Neuroscience · doi:10.1038/nn.2600 · Cited by 258
“For example, the basic helix-loop-helix (bHLH) transcription factors Olig1 and Olig2 have been implicated in oligodendrogenesis and neurogenesi”
Background
RESEARCH ARTICLE: Myelin Abnormalities without Oligodendrocyte Loss in Periventricular Leukomalacia
Billiards, S., Haynes, R., Folkerth, R., Borenstein, N. S., Trachtenberg, F., Rowitch, D., Ligon, K., Volpe, J., & Kinney, H. C. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00107.x · Cited by 257
Cell fate specification in the mammalian telencephalon
Guillemot, F. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.02.009 · Cited by 248
Peripheral nerve-derived VEGF promotes arterial differentiation via neuropilin 1-mediated positive feedback
Mukouyama, Y., Gerber, H., Ferrara, N., Gu, C.-H., & Anderson, D. J. (2005) · Development · doi:10.1242/dev.01675 · Cited by 255
Self-citation
Specification of temporal identity in the developing nervous system.
Pearson, B. J., & Doe, C. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.19.111301.115142 · Cited by 254
“In olig2 mutants, ventral progenitors are transformed to a more dorsal fate, yet they still undergo their normal temporal program of differentiation, generating V2 interneurons early and astrocytes late (Lu et al. 2002, Zhou & Anderson 2002).”
Background
Myelinogenesis and Axonal Recognition by Oligodendrocytes in Brain Are Uncoupled inOlig1-Null Mice
Xin, M., Yue, T., Ma, Z., Wu, F.-F., Gow, A., & Lu, Q. R. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3034-04.2005 · Cited by 267
“Importantly, oligodendrocytes are absent in all brain regions of Olig1;Olig2-null double mutants, which demonstrates the critical functions of these genes during development (Lu et al., 2002; Zhou and Anderson, 2002).”
BackgroundInfluential
Olig2 Directs Astrocyte and Oligodendrocyte Formation in Postnatal Subventricular Zone Cells
Marshall, C. A. G., Novitch, B. G., & Goldman, J. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1924-05.2005 · Cited by 249
“The Olig2 constructs used for functional experiments are specific (Novitch et al., 2001; Zhou and Anderson, 2002; Gabay et al., 2003).”
Method
Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors.Preprint
Pattyn, A., Vallstedt, A., Dias, J. M., Samad, O. A., Krumlauf, R., Rijli, F., Brunet, J., & Ericson, J. (2003) · Genes & Development · doi:10.1101/gad.255803 · Cited by 247
“However, the precise role of these proteins in this switch remains unclear, because a neuron-to-glial switch is still observed in both Nkx2.2 (Qi et al. 2001) and Olig2 (Lu et al. 2002; Zhou and Anderson 2002 ) mutant mice.”
Background
Oxidative stress disrupts oligodendrocyte maturation
French, H. M., Reid, M., Mamontov, P., Simmons, R. A., & Grinspan, J. B. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22139 · Cited by 246
Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus
Chetty, S., Friedman, A. R., Taravosh‐Lahn, K., Kirby, E. D., Mirescu, C., Guo, F., Krupik, D., Nicholas, A. C., Geraghty, A. C., Krishnamurthy, A., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.190 · Cited by 237

Authors: Zhou, Q., & Anderson, D. J.
Affiliations: California Institute of Technology (US)
Corresponding author: Anderson, David J.
ORCID: Zhou, Qiao
Anderson, David J.
Venue: Cell
Publisher: Elsevier BV
Published: 2002-04
Volume: 109
Issue: 1
Pages: 61-73
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(02)00677-3
OpenAlex: W2125920059
Cited by: 1,059
References: 70
Citations by year: 2026: 16 · 2025: 27 · 2024: 29 · 2023: 27 · 2022: 45 · 2021: 46 · 2020: 26 · 2019: 36 · 2018: 36 · 2017: 36 · 2016: 33 · 2015: 41 · 2014: 52 · 2013: 48 · 2012: 52
FWCI: 14.68
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4125 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01-NS23476, R01NS023476)
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords: Olig2, Olig1, bHLH transcription factors, motor neurons, oligodendrocytes, astrocytes, proneural genes, lineage tracing
MeSH terms: Oligodendrocyte Transcription Factor 2, Animals, Astrocytes, Cell Differentiation, DNA-Binding Proteins, Female, Interneurons, Male, Motor Neurons, Mutation, Nerve Tissue Proteins, Neuroglia, Neurons, Oligodendroglia, Rhombencephalon, Spinal Cord, Stem Cells, Transcription Factors, Helix-Loop-Helix Motifs, Mice, Knockout, Homeodomain Proteins, Cell Lineage, Mice, Basic Helix-Loop-Helix Proteins

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The bHLH Transcription Factors OLIG2 and OLIG1 Couple Neuronal and Glial Subtype Specification

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