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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Background
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“OLIG2 is a neural stem cell transcription factor that regulates the differentiation of oligodendrocytes (Zhou & Anderson 2002).”
Background
Expression profiles of inka2 in the murine nervous system
Iwasaki, Y., Yumoto, T., & Sakakibara, S. (2015) · Gene Expression Patterns · doi:10.1016/j.gep.2015.08.002 · Cited by 15
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“…domains, p3 and pMN, generate V3 interneurons and motor neurons (MNs), respectively, and they are distinguished and specified by expression of the transcription factors Nkx2-2 and Olig2 (Briscoe et al., 1999; Mizuguchi et al., 2001; Novitch et al., 2001; Lu et al., 2002; Zhou and Anderson, 2002).”
Background
Delayed Onset of Experimental Autoimmune Encephalomyelitis in Olig1 Deficient Mice
Guo, X., Harada, C., Namekata, K., Mitamura, Y., Yoshida, H., Matsumoto, Y., & Harada, T. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013083 · Cited by 16
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A bipotent neural progenitor cell line cloned from a cerebellum of an adult p53‐deficient mouse generates both neurons and oligodendrocytes
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“Olig1 and Olig2 have been identified as related transcription factors in oligodendrocyte development, and double knockouts of the genes affect both motoneuron and oligodendrocyte development (Lu et al., 2000; Zhou et al., 2000; Lu et al., 2002; Zhou & Anderson, 2002).”
BackgroundMethod
Plasticity as a therapeutic target for improving cognition and behavior in Down syndrome
Martínez‐Cué, C., & Dierssen, M. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.11.001 · Cited by 15
Mechanisms of astrocyte development
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Identity and Maturity of iPSC-Derived Oligodendrocytes in 2D and Organoid Systems
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“Loss of functions of OLIG2 completely abolishes oligo-dendrocyte lineage commitment and development [14,15] and the expression of NKX2.”
Background
Evolution and Development of Extra-Ocular Nerves and Muscles in Vertebrates
Fritzsch, B. (2023) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2024.152225 · Cited by 23
Biological functions of the Olig gene family in brain cancer and therapeutic targeting
Szu, J., Tsigelny, I., Wojcinski, A., & Kesari, S. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1129434 · Cited by 15
“It was shown that Olig1/2 may promote astrocyte differentiation where astrocytes are sequentially transformed after generation of interneurons (Zhou and Anderson, 2002).”
Background
Cellular diversity and developmental hierarchy in the planarian nervous system
Wyss, L. S., Bray, S. R., & Wang, B. (2022) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2022.101960 · Cited by 16
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The Chromatin Environment Around Interneuron Genes in Oligodendrocyte Precursor Cells and Their Potential for Interneuron Reprograming
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“During mid-embryonic development, OPCs arise in discrete domains in the ventral germinal zones, and this process is dependent on the basic helix-loop-helix (bHLH) transcription factor Olig2 (Lu et al., 2002; Takebayashi et al., 2002; Zhou and Anderson, 2002).”
Background
Cis-topic modelling of single-cell epigenomesPreprint
González-Blas, C., Minnoye, L., Papasokrati, D., Aibar, S., Hulselmans, G., Christiaens, V., Davie, K., Wouters, J., & Aerts, S. (2018) · bioRxiv · doi:10.1101/370346 · Cited by 15
“SOX10, OLIG1 and OLIG2 are master regulators of oligodendrocyte development (Wegner and Stolt, 2005; Yu et al., 2013; Zhou and Anderson, 2002) , and NEUROD1/2 is a marker of granule cell differentiation (Miyata et al., 1999).”
Background
Basic Helix–Loop–Helix Proteins Expressed During Early Embryonic Organogenesis
Hjalt, T. Å. H. (2004) · International review of cytology · doi:10.1016/s0074-7696(04)36006-7 · Cited by 16
Identification of genome-wide targets of Olig2 in the adult mouse spinal cord using ChIP-Seq
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Deterioration of neuroimmune homeostasis in Alzheimer’s Disease patients who survive a COVID-19 infection
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A novel protocol to derive cervical motor neurons from induced pluripotent stem cells for amyotrophic lateral sclerosis
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“Compound E effectively promotes the conversion of MNPs into sMNs In the pMN domain, OLIG2-expressing MNPs can become MNs or oligodendrocytes (Lu et al., 2002; Zhou and Anderson, 2002).”
Maternal separation with early weaning impairs neuron-glia integrity: non-invasive evaluation and substructure demonstration
Zeng, H., Zhang, X., Wang, W., Shen, Z., Dai, Z., Yu, Z., Xu, S., Yan, G., Huang, Q., Wu, R., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-76640-y · Cited by 18
Zebrafish prdm12b acts independently of nkx6.1 repression to promote eng1b expression in the neural tube p1 domain
Yildiz, O., Downes, G. B., & Sagerström, C. G. (2019) · Neural Development · doi:10.1186/s13064-019-0129-x · Cited by 20
“For instance, Irx3 and Olig2 are mutually repressive at the p2/ pMN boundary [8, 14] such that loss of Olig2 leads to a ventral expansion of Irx3 expression, causing the pMN domain to give rise to V2 interneurons and astrocytes in place of motor neurons and oligodendrocytes [14].”
An emerging role for prdm family genes in dorsoventral patterning of the vertebrate nervous system
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TIP30 inhibits oligodendrocyte precursor cell differentiation via cytoplasmic sequestration of Olig1
Yang, W., Xiao, L., Li, C., Liu, X., Liu, M., Shao, Q., Wang, D., Huang, A., & He, C. (2014) · Glia · doi:10.1002/glia.22778 · Cited by 15
Cytochrome P450 Cyp26a1 Alters Spinal Motor Neuron Subtype Identity in Differentiating Embryonic Stem Cells*
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Teratogenic Potential in Cultures Optimized for Oligodendrocyte Development from Mouse Embryonic Stem Cells
Sadowski, D. H., Kiel, M. E., Apicella, M., Arriola, A. G. P., Chen, C. P., & McKinnon, R. D. (2010) · Stem Cells and Development · doi:10.1089/scd.2009.0520 · Cited by 14
“2 and Olig2, which can induce OPCs from non-pMN foci in the chick neural tube [ 45 ].”
Differential expression and regulation of olig genes in zebrafish
Tiso, N., Filippi, A., Benato, F., Negrisolo, E., Modena, N., Vaccari, E., Driever, W., & Argenton, F. (2009) · The Journal of comparative neurology · doi:10.1002/cne.22054 · Cited by 14
Nkx2.2 Expression in Differentiation of Oligodendrocyte Precursor Cells and Inhibitory Factors for Differentiation of Oligodendrocytes after Traumatic Spinal Cord Injury
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Oligodendrogenesis in Evolution, Development and Adulthood
Hu, H., Gao, T., Zhao, J., & Li, H. (2025) · Glia · doi:10.1002/glia.70033 · Cited by 16
“…factors that are important to oligodendrocyte specification include basic helix–loop–helix (bHLH) proteins Olig1/Olig2 (Lu et al. 2002; Zhou and Anderson 2002) and SRY-related HMG-box E (SoxE) proteins Sox8/Sox9/Sox10 (with functional redundancy) (Finzsch et al. 2008; Stolt et al.…”
Developmental stage of transplanted neural progenitor cells influences anatomical and functional outcomes after spinal cord injury in mice
Aceves, M., Tucker, A., Chen, J., Vo, K., Moses, J., Kumar, P. A., Thomas, H., Miranda, D., Dampf, G., Dietz, V. A., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04893-0 · Cited by 13
Characterization of immature ovarian teratomas through single-cell transcriptome
Cao, M., Deng, Y. K., Deng, Y., Wu, J., Yang, C., Wang, Z., Hou, Q., Fu, H., Ren, Z., Xia, X., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1131814 · Cited by 13
“, OLIG1, OLIG2, APOD, and S100B) (45) (Figures 3F, G), while expression of S100B and SCRG1 exhibited negative correlation with immature neuron proportions in CDTs (Supplementary Figure 3G).”
Background
The Shh/Gli1 signaling pathway regulates regeneration via transcription factor Olig1 expression after focal cerebral ischemia in rats
Zhao, H., Gao, X.-Y., Wu, X., Zhang, Y., & Wang, X.-F. (2021) · Neurological Research · doi:10.1080/01616412.2021.1981106 · Cited by 14
Ddx20, DEAD box helicase 20, is essential for the differentiation of oligodendrocyte and maintenance of myelin gene expression
Simankova, A., Bizen, N., Saitoh, S., Shibata, S., Ohno, N., Abe, M., Sakimura, K., & Takebayashi, H. (2021) · Glia · doi:10.1002/glia.24058 · Cited by 17
“…or oligodendrocyte terminal differentiation; for example, Olig2 is involved in OPC specification (Lu et al., 2002; Takebayashi et al., 2002; Q. Zhou & Anderson, 2002), whereas Myrf (Emery et al., 2009) and Sox10 (Stolt et al., 2002) are involved in the transcription of myelin-related genes.”
Background
Cracking the Codes of Cortical Glial Progenitors: Evidence for the Common Lineage of Astrocytes and Oligodendrocytes
Huang, H., Rubenstein, J., & Qiu, M.-S. (2021) · Neuroscience Bulletin · doi:10.1007/s12264-021-00675-y · Cited by 13
“In the developing spinal cord, analysis of the Olig genes demonstrated that OPCs and astrocytes originate from distinct domains of neural progenitor cells (NPCs) [4,5].”
Background
WNT signaling suppresses oligodendrogenesis via Ngn2-dependent direct inhibition of Olig2 expression
Jiang, M., Yu, D., Xie, B., Huang, H., Lu, W., Qiu, M.-S., & Dai, Z.-M. (2020) · Molecular Brain · doi:10.1186/s13041-020-00696-0 · Cited by 13
Strong sonic hedgehog signaling in the mouse ventral spinal cord is not required for oligodendrocyte precursor cell (OPC) generation but is necessary for correct timing of its generation
Hashimoto, H., Jiang, W. J., Yoshimura, T., Moon, K.-H., Bok, J., & Ikenaka, K. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.11.003 · Cited by 17
“In the absence of Olig2, neither motor neurons nor oligodendrocytes are produced (Lu et al., 2002; Takebayashi et al., 2002; Zhou and Anderson, 2002).”
Olig2 is expressed late in human eosinophil development and controls Siglec-8 expression
Hwang, S. M., Uhm, T. G., Lee, S. K., Kong, S.-K., Jung, K. H., Binas, B., Chai, Y. G., Park, S., & Chung, I. Y. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.1a0715-314rrr · Cited by 16
Deletion of the App-Runx1 region in mice models human partial monosomy 21
Arbogast, T., Raveau, M., Chevalier, C., Nalesso, V., Dembélé, D., Jacobs, H., Wendling, O., Roux, M., Duchon, A., & Hérault, Y. (2015) · Disease Models & Mechanisms · doi:10.1242/dmm.017814 · Cited by 13
“In Olig1- and Olig2deficient mice, motoneurons are converted to V2 interneurons in the spinal cord, and oligodendrocytes fail to differentiate throughout the nervous system (Zhou and Anderson, 2002).”
Finding degrees of separation: Experimental approaches for astroglial and oligodendroglial cell isolation and genetic targeting
Chew, L., DeBoy, C. A., & Senatorov, V. V. (2014) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2014.08.017 · Cited by 13

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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