OLIG2

Last updated
OLIG2
Identifiers
Aliases OLIG2 , BHLHB1, OLIGO2, PRKCBP2, RACK17, bHLHe19, oligodendrocyte lineage transcription factor 2, oligodendrocyte transcription factor 2
External IDs OMIM: 606386; MGI: 1355331; HomoloGene: 4241; GeneCards: OLIG2; OMA:OLIG2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

10215

50913

Ensembl

ENSG00000205927

ENSMUSG00000039830

UniProt

Q13516

Q9EQW6

RefSeq (mRNA)

NM_005806

NM_016967

RefSeq (protein)

NP_005797

NP_058663

Location (UCSC) Chr 21: 33.03 – 33.03 Mb Chr 16: 91.02 – 91.03 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Oligodendrocyte transcription factor (OLIG2) is a basic helix-loop-helix (bHLH) transcription factor encoded by the OLIG2 gene. The protein is of 329 amino acids in length, 32 kDa in size and contains one basic helix-loop-helix DNA-binding domain. [5] It is one of the three members of the bHLH family. The other two members are OLIG1 and OLIG3. The expression of OLIG2 is mostly restricted in central nervous system, where it acts as both an anti-neurigenic and a neurigenic factor at different stages of development. OLIG2 is well known for determining motor neuron and oligodendrocyte differentiation, as well as its role in sustaining replication in early development. It is mainly involved in diseases such as brain tumor and Down syndrome.

Contents

Function

OLIG2 is mostly expressed in restricted domains of the brain and spinal cord ventricular zone which give rise to oligodendrocytes and specific types of neurons. In the spinal cord, the pMN region sequentially generates motor neurons and oligodendrocytes. During embryogenesis, OLIG2 first directs motor neuron fate by establishing a ventral domain of motor neuron progenitors and promoting neuronal differentiation. OLIG2 then switches to promoting the formation of oligodendrocyte precursors and oligodendrocyte differentiation at later stages of development. Apart from functioning as a neurogenic factor in specification and the differentiation of motor neurons and oligodendrocytes, OLIG2 also functions as an anti-neurogenic factor at early time points in pMN progenitors to sustain the cycling progenitor pool. This side of anti-neurogenicity of OLIG2 later plays a bigger role in malignancies like glioma. [6]

The role of phosphorylation has been highlighted recently to account for the multifaceted functions of OLIG2 in differentiation and proliferation. Studies showed that the phosphorylation state of OLIG2 at Ser30 determines the fate of cortical progenitor cells, in which cortical progenitor cells will either differentiate into astrocytes or remain as neuronal progenitors. [7] Phosphorylation at a triple serine motif (Ser10, Ser13 and Ser14) on the other hand was shown to regulate the proliferative function of OLIG2. [8] Another phosphorylation site Ser147 predicted by bioinformatics was found to regulate motor neuron development by regulating the binding between OLIG2 and NGN2. [9] Further, OLIG2 contains a ST box composed of a string of 12 contiguous serine and threonine residues at position Ser77-Ser88. It is believed that phosphorylation at ST box is biologically functional, [10] yet the role of it still remains to be elucidated in vivo. [11]

OLIG2 has also been implicated in bovine horn ontogenesis. It was the only gene in the bovine polled locus to show differential expression between the putative horn bud and the frontal forehead skin. [12]

Clinical Significance

OLIG2 in Cancer

OLIG2 is well recognized for its importance in cancer research, particularly in brain tumors and leukemia. OLIG2 is universally expressed in glioblastoma and other diffuse gliomas (astrocytomas, oligodendrogliomas and oligoastrocytomas), and is a useful positive diagnostic marker of these brain tumors. [13] Although in normal brain tissue OLIG2 expresses mostly on oligodendrocytes but not on mature astrocytes, in adult glioma, OLIG2 expresses on both IDH1 or IDH2-mutant adult lower grade astrocytoma and oligodendroglioma on similar levels, but it is expressed on a lower level on IDH-wildtype glioblastoma. [14] OLIG2 overexpression is a good surrogate marker for IDH mutation with an AUC of 0.90, but predicts poorly (AUC = 0.55) for 1p/19q co-deletion, a class-defining chromosomal alteration for oligodendroglioma. [14] In survival analysis, higher mRNA levels of OLIG2 were associated with better overall survival, but this association was completely dependent on IDH mutation status. [14]

In particular, OLIG2 is selectively expressed in a subgroup of glioma cells that are highly tumorigenic, [15] and is shown to be required for proliferation of human glioma cells implanted in the brain of severe combined immunodeficiency (SCID) mice. [16]

Though the molecular mechanism behind this tumorigenesis is not entirely clear, more studies have recently been published pinpointing diverse evidence and potential roles for OLIG2 in glioma progression. It is believed that OLIG2 promotes neural stem cell and progenitor cell proliferation by opposing p53 pathway, which potentially contributes to glioma progression. OLIG2 has been shown to directly repress the p53 tumor-suppressor pathway effector p21WAF1/CIP1, [17] suppress p53 acetylation and impede the binding of p53 to several enhancer sites. [18] It is further found that the phosphorylation of triple-serine motif in OLIG2 is present in several glioma lines and is more tumorigenic than the unphosphorylated status. [19] In a study using the U12-1 cell line for controlled expression of OLIG2, researchers showed that OLIG2 can suppress the proliferation of U12-1 by transactivating the p27Kip1 gene [20] and can inhibit the motility of the cell by activating RhoA. [21]

Besides glioma, OLIG2 is also involved in leukemogenesis. The Olig2 gene was actually first identified in a study in T-cell acute lymphoblastic leukemia, in which the expression of OLIG2 was found elevated after t(14;21)(q11.2;q22) chromosomal translocation. [22] The overexpression of OLIG2 was later shown present in malignancies beyond glioma and leukemia, such as breast cancer, melanoma and non-small cell lung carcinoma cell lines. [23] It also has been shown that up-regulation of OLIG2 together with LMO1 and Notch1 helps to provide proliferation signals.

OLIG2 in Neural Diseases

OLIG2 is also associated with Down syndrome, as it locates at chromosome 21 within or near the Down syndrome critical region on the long arm. This region is believed to contribute to the cognitive defects of Down syndrome. The substantial increase in the number of forebrain inhibitory neurons often observed in Ts65dn mouse (a murine model of trisomy 21) could lead to imbalance between excitation and inhibition and behavioral abnormalities. However, genetic reduction of OLIG2 and OLIG1 from three copies to two rescued the overproduction of interneurons, indicating the pivotal role of OLIG2 expression level in Down syndrome. [24] The association between OLIG2 and neural diseases (i.e. schizophrenia and Alzheimer's disease) are under scrutiny, as several single nucleotide polymorphisms (SNPs) associated with these diseases in OLIG2 were identified by genome-wide association work. [25] [26]

OLIG2 also plays a functional role in neural repair. Studies showed that the number of OLIG2-expressing cells increased in the lesion after cortical stab-wound injury, supporting the role for OLIG2 in reactive gliosis. [27] OLIG2 was also implicated in generating reactive astrocytes possibly in a transient re-expression manner, but the mechanisms are unclear. [28]

Related Research Articles

<span class="mw-page-title-main">Oligodendrocyte</span> Neural cell type

Oligodendrocytes, also known as oligodendroglia, are a type of neuroglia whose main function is to provide the myelin sheath to neuronal axons in the central nervous system (CNS). Myelination gives metabolic support to, and insulates the axons of most vertebrates. A single oligodendrocyte can extend its processes to cover up to 40 axons, that can include multiple adjacent axons. The myelin sheath is not continuous but is segmented along the axon's length at gaps known as the nodes of Ranvier. In the peripheral nervous system the myelination of axons is carried out by Schwann cells.

Oligodendrocyte progenitor cells (OPCs), also known as oligodendrocyte precursor cells, NG2-glia, O2A cells, or polydendrocytes, are a subtype of glia in the central nervous system named for their essential role as precursors to oligodendrocytes and myelin. They are typically identified in the human by co-expression of PDGFRA and CSPG4.

Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor stem cells persist in highly restricted regions in the adult vertebrate brain and continue to produce neurons throughout life. Differences in the size of the central nervous system are among the most important distinctions between the species and thus mutations in the genes that regulate the size of the neural stem cell compartment are among the most important drivers of vertebrate evolution.

<span class="mw-page-title-main">Radial glial cell</span> Bipolar-shaped progenitor cells of all neurons in the cerebral cortex and some glia

Radial glial cells, or radial glial progenitor cells (RGPs), are bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including astrocytes and oligodendrocytes. Their cell bodies (somata) reside in the embryonic ventricular zone, which lies next to the developing ventricular system.

<span class="mw-page-title-main">Subventricular zone</span> Region outside each lateral ventricle of the brain

The subventricular zone (SVZ) is a region situated on the outside wall of each lateral ventricle of the vertebrate brain. It is present in both the embryonic and adult brain. In embryonic life, the SVZ refers to a secondary proliferative zone containing neural progenitor cells, which divide to produce neurons in the process of neurogenesis. The primary neural stem cells of the brain and spinal cord, termed radial glial cells, instead reside in the ventricular zone (VZ).

<span class="mw-page-title-main">TEAD2</span> Protein-coding gene in the species Homo sapiens

TEAD2, together with TEAD1, defines a novel family of transcription factors, the TEAD family, highly conserved through evolution. TEAD proteins were notably found in Drosophila (Scalloped), C. elegans, S. cerevisiae and A. nidulans. TEAD2 has been less studied than TEAD1 but a few studies revealed its role during development.

<span class="mw-page-title-main">SOX2</span> Transcription factor gene of the SOX family

SRY -box 2, also known as SOX2, is a transcription factor that is essential for maintaining self-renewal, or pluripotency, of undifferentiated embryonic stem cells. Sox2 has a critical role in maintenance of embryonic and neural stem cells.

<span class="mw-page-title-main">Protein BTG2</span> Protein-coding gene in the species Homo sapiens

Protein BTG2 also known as BTG family member 2 or NGF-inducible anti-proliferative protein PC3 or NGF-inducible protein TIS21, is a protein that in humans is encoded by the BTG2 gene and in other mammals by the homologous Btg2 gene. This protein controls cell cycle progression and proneural genes expression by acting as a transcription coregulator that enhances or inhibits the activity of transcription factors.

<span class="mw-page-title-main">ISL1</span> Protein-coding gene in the species Homo sapiens

Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the ISL1 gene.

<span class="mw-page-title-main">NFIX</span> Protein-coding gene in the species Homo sapiens

Nuclear factor 1 X-type is a protein that in humans is encoded by the NFIX gene. NFI-X3, a splice variant of NFIX, regulates Glial fibrillary acidic protein and YKL-40 in astrocytes.

<span class="mw-page-title-main">OLIG1</span> Protein-coding gene in the species Homo sapiens

Oligodendrocyte transcription factor 1 is a protein that in humans is encoded by the OLIG1 gene.

Neurogenins, often abbreviated as Ngn, are a family of bHLH transcription factors involved in specifying neuronal differentiation. The family consisting of Neurogenin-1, Neurogenin-2, and Neurogenin-3, plays a fundamental role in specifying neural precursor cells and regulating the differentiation of neurons during embryonic development. It is one of many gene families related to the atonal gene in Drosophila. Other positive regulators of neuronal differentiation also expressed during early neural development include NeuroD and ASCL1.

<span class="mw-page-title-main">NKX2-2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Nkx-2.2 is a protein that in humans is encoded by the NKX2-2 gene.

<span class="mw-page-title-main">Myelin regulatory factor</span> Mammalian protein found in Homo sapiens

Myelin regulatory factor, also known as myelin gene regulatory factor (MRF), is a protein that in humans is encoded by the MYRF gene.

<span class="mw-page-title-main">Hes3 signaling axis</span>

The STAT3-Ser/Hes3 signaling axis is a specific type of intracellular signaling pathway that regulates several fundamental properties of cells.

Proneural genes encode transcription factors of the basic helix-loop-helix (bHLH) class which are responsible for the development of neuroectodermal progenitor cells. Proneural genes have multiple functions in neural development. They integrate positional information and contribute to the specification of progenitor-cell identity. From the same ectodermal cell types, neural or epidermal cells can develop based on interactions between proneural and neurogenic genes. Neurogenic genes are so called because loss of function mutants show an increase number of developed neural precursors. On the other hand, proneural genes mutants fail to develop neural precursor cells.

<span class="mw-page-title-main">Neuronal lineage marker</span> Endogenous tag expressed in different cells along neurogenesis and differentiated cells

A neuronal lineage marker is an endogenous tag that is expressed in different cells along neurogenesis and differentiated cells such as neurons. It allows detection and identification of cells by using different techniques. A neuronal lineage marker can be either DNA, mRNA or RNA expressed in a cell of interest. It can also be a protein tag, as a partial protein, a protein or an epitope that discriminates between different cell types or different states of a common cell. An ideal marker is specific to a given cell type in normal conditions and/or during injury. Cell markers are very valuable tools for examining the function of cells in normal conditions as well as during disease. The discovery of various proteins specific to certain cells led to the production of cell-type-specific antibodies that have been used to identify cells.

<span class="mw-page-title-main">Gloria Choi</span> South Korean neuroscientist and neuroimmunologist

Gloria Choi is an American neuroscientist and neuroimmunologist and the Samuel A. Goldblith Career Development Professor in the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology. Choi is known for elucidating the role of the immune system in the development of autism spectrum disorder-like phenotypes. Her lab currently explores how sensory experiences drive internal states and behavioural outcomes through probing the olfactory system as well as the neuroimmune system.

David Rowitch, FMedSci, FRS is an American physician-scientist known for his contributions to developmental glial biology and treatment of white matter diseases. He heads the Department of Paediatrics at the University of Cambridge and is an adjunct professor of pediatrics at the University of California San Francisco (UCSF).

A myelinoid or myelin organoid is a three dimensional in vitro cultured model derived from human pluripotent stem cells (hPSCs) that represents various brain regions, the spinal cord or the peripheral nervous system in early fetal human development. Myelinoids have the capacity to recapitulate aspects of brain developmental processes, microenvironments, cell to cell interaction, structural organization and cellular composition. The differentiating aspect dictating whether an organoid is deemed a cerebral organoid/brain organoid or myelinoid is the presence of myelination and compact myelin formation that is a defining feature of myelinoids. Due to the complex nature of the human brain, there is a need for model systems which can closely mimic complicated biological processes. Myelinoids provide a unique in vitro model through which myelin pathology, neurodegenerative diseases, developmental processes and therapeutic screening can be accomplished.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000205927 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000039830 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "OLIG2". Atlas of Genetics and Cytogenetics in Oncology and Hematology.
  6. ↑ Gaber ZB, Novitch BG (Mar 2011). "All the embryo's a stage, and Olig2 in its time plays many parts". Neuron. 69 (5): 833–5. doi: 10.1016/j.neuron.2011.02.037 . PMID   21382543. S2CID   18323261.
  7. ↑ Setoguchi T, Kondo T (Sep 2004). "Nuclear export of OLIG2 in neural stem cells is essential for ciliary neurotrophic factor-induced astrocyte differentiation". The Journal of Cell Biology. 166 (7): 963–8. doi:10.1083/jcb.200404104. PMC   2172021 . PMID   15452140.
  8. ↑ Sun Y, Meijer DH, Alberta JA, Mehta S, Kane MF, Tien AC, Fu H, Petryniak MA, Potter GB, Liu Z, Powers JF, Runquist IS, Rowitch DH, Stiles CD (Mar 2011). "Phosphorylation state of Olig2 regulates proliferation of neural progenitors". Neuron. 69 (5): 906–17. doi:10.1016/j.neuron.2011.02.005. PMC   3065213 . PMID   21382551.
  9. ↑ Li H, de Faria JP, Andrew P, Nitarska J, Richardson WD (Mar 2011). "Phosphorylation regulates OLIG2 cofactor choice and the motor neuron-oligodendrocyte fate switch". Neuron. 69 (5): 918–29. doi:10.1016/j.neuron.2011.01.030. PMC   3093612 . PMID   21382552.
  10. ↑ Huillard E, Ziercher L, Blond O, Wong M, Deloulme JC, Souchelnytskyi S, Baudier J, Cochet C, Buchou T (Jun 2010). "Disruption of CK2beta in embryonic neural stem cells compromises proliferation and oligodendrogenesis in the mouse telencephalon". Molecular and Cellular Biology. 30 (11): 2737–49. doi:10.1128/MCB.01566-09. PMC   2876519 . PMID   20368359.
  11. ↑ Sun Y, Meijer DH, Alberta JA, Mehta S, Kane MF, Tien AC, Fu H, Petryniak MA, Potter GB, Liu Z, Powers JF, Runquist IS, Rowitch DH, Stiles CD (Mar 2011). "Phosphorylation state of Olig2 regulates proliferation of neural progenitors". Neuron. 69 (5): 906–17. doi:10.1016/j.neuron.2011.02.005. PMC   3065213 . PMID   21382551.
  12. ↑ Allais-Bonnet A, Grohs C, Medugorac I, Krebs S, Djari A, Graf A, Fritz S, Seichter D, Baur A, Russ I, Bouet S, Rothammer S, Wahlberg P, Esquerré D, Hoze C, Boussaha M, Weiss B, Thépot D, Fouilloux MN, Rossignol MN, van Marle-Köster E, Hreiðarsdóttir GE, Barbey S, Dozias D, Cobo E, Reversé P, Catros O, Marchand JL, Soulas P, Roy P, Marquant-Leguienne B, Le Bourhis D, Clément L, Salas-Cortes L, Venot E, Pannetier M, Phocas F, Klopp C, Rocha D, Fouchet M, Journaux L, Bernard-Capel C, Ponsart C, Eggen A, Blum H, Gallard Y, Boichard D, Pailhoux E, Capitan A (2013). "Novel insights into the bovine polled phenotype and horn ontogenesis in Bovidae". PLOS ONE. 8 (5): e63512. Bibcode:2013PLoSO...863512A. doi: 10.1371/journal.pone.0063512 . PMC   3661542 . PMID   23717440.
  13. ↑ Ligon KL, Alberta JA, Kho AT, Weiss J, Kwaan MR, Nutt CL, Louis DN, Stiles CD, Rowitch DH (May 2004). "The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas". Journal of Neuropathology and Experimental Neurology. 63 (5): 499–509. doi:10.1093/jnen/63.5.499. PMID   15198128.
  14. 1 2 3 Mo H, Magaki S, Deisch JK, Raghavan R (August 2022). "Isocitrate Dehydrogenase Mutations Are Associated with Different Expression and DNA Methylation Patterns of OLIG2 in Adult Gliomas". Journal of Neuropathology and Experimental Neurology. 81 (9): 707–716. doi:10.1093/jnen/nlac059. PMC   9614687 . PMID   35856894.
  15. ↑ Ligon KL, Huillard E, Mehta S, Kesari S, Liu H, Alberta JA, Bachoo RM, Kane M, Louis DN, Depinho RA, Anderson DJ, Stiles CD, Rowitch DH (Feb 2007). "Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma". Neuron. 53 (4): 503–17. doi:10.1016/j.neuron.2007.01.009. PMC   1810344 . PMID   17296553.
  16. ↑ Mehta S, Huillard E, Kesari S, Maire CL, Golebiowski D, Harrington EP, Alberta JA, Kane MF, Theisen M, Ligon KL, Rowitch DH, Stiles CD (Mar 2011). "The central nervous system-restricted transcription factor Olig2 opposes p53 responses to genotoxic damage in neural progenitors and malignant glioma". Cancer Cell. 19 (3): 359–71. doi:10.1016/j.ccr.2011.01.035. PMC   3070398 . PMID   21397859.
  17. ↑ Ligon KL, Huillard E, Mehta S, Kesari S, Liu H, Alberta JA, Bachoo RM, Kane M, Louis DN, Depinho RA, Anderson DJ, Stiles CD, Rowitch DH (Feb 2007). "Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma". Neuron. 53 (4): 503–17. doi:10.1016/j.neuron.2007.01.009. PMC   1810344 . PMID   17296553.
  18. ↑ Mehta S, Huillard E, Kesari S, Maire CL, Golebiowski D, Harrington EP, Alberta JA, Kane MF, Theisen M, Ligon KL, Rowitch DH, Stiles CD (Mar 2011). "The central nervous system-restricted transcription factor Olig2 opposes p53 responses to genotoxic damage in neural progenitors and malignant glioma". Cancer Cell. 19 (3): 359–71. doi:10.1016/j.ccr.2011.01.035. PMC   3070398 . PMID   21397859.
  19. ↑ Sun Y, Meijer DH, Alberta JA, Mehta S, Kane MF, Tien AC, Fu H, Petryniak MA, Potter GB, Liu Z, Powers JF, Runquist IS, Rowitch DH, Stiles CD (Mar 2011). "Phosphorylation state of Olig2 regulates proliferation of neural progenitors". Neuron. 69 (5): 906–17. doi:10.1016/j.neuron.2011.02.005. PMC   3065213 . PMID   21382551.
  20. ↑ Tabu K, Ohnishi A, Sunden Y, Suzuki T, Tsuda M, Tanaka S, Sakai T, Nagashima K, Sawa H (Apr 2006). "A novel function of OLIG2 to suppress human glial tumor cell growth via p27Kip1 transactivation". Journal of Cell Science. 119 (Pt 7): 1433–41. doi:10.1242/jcs.02854. PMID   16554441. S2CID   14374119.
  21. ↑ Tabu K, Ohba Y, Suzuki T, Makino Y, Kimura T, Ohnishi A, Sakai M, Watanabe T, Tanaka S, Sawa H (Oct 2007). "Oligodendrocyte lineage transcription factor 2 inhibits the motility of a human glial tumor cell line by activating RhoA". Molecular Cancer Research. 5 (10): 1099–109. doi: 10.1158/1541-7786.MCR-07-0096 . PMID   17951409.
  22. ↑ Birdsall B, Griffiths DV, Roberts GC, Feeney J, Burgen A (Mar 1977). "1H nuclear magnetic resonance studies of Lactobacillus casei dihydrofolate reductase: effects of substrate and inhibitor binding on the histidine residues". Proceedings of the Royal Society of London. Series B, Biological Sciences. 196 (1124): 251–65. Bibcode:1977RSPSB.196..251B. doi:10.1098/rspb.1977.0040. PMID   16268. S2CID   1651311.
  23. ↑ Lin YW, Deveney R, Barbara M, Iscove NN, Nimer SD, Slape C, Aplan PD (Aug 2005). "OLIG2 (BHLHB1), a bHLH transcription factor, contributes to leukemogenesis in concert with LMO1". Cancer Research. 65 (16): 7151–8. doi:10.1158/0008-5472.CAN-05-1400. PMC   1681523 . PMID   16103065.
  24. ↑ Chakrabarti L, Best TK, Cramer NP, Carney RS, Isaac JT, Galdzicki Z, Haydar TF (Aug 2010). "Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome". Nature Neuroscience. 13 (8): 927–34. doi:10.1038/nn.2600. PMC   3249618 . PMID   20639873.
  25. ↑ Georgieva L, Moskvina V, Peirce T, Norton N, Bray NJ, Jones L, Holmans P, Macgregor S, Zammit S, Wilkinson J, Williams H, Nikolov I, Williams N, Ivanov D, Davis KL, Haroutunian V, Buxbaum JD, Craddock N, Kirov G, Owen MJ, O'Donovan MC (Aug 2006). "Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia". Proceedings of the National Academy of Sciences of the United States of America. 103 (33): 12469–74. Bibcode:2006PNAS..10312469G. doi: 10.1073/pnas.0603029103 . PMC   1567903 . PMID   16891421.
  26. ↑ Sims R, Hollingworth P, Moskvina V, Dowzell K, O'Donovan MC, Powell J, Lovestone S, Brayne C, Rubinsztein D, Owen MJ, Williams J, Abraham R (Sep 2009). "Evidence that variation in the oligodendrocyte lineage transcription factor 2 (OLIG2) gene is associated with psychosis in Alzheimer's disease". Neuroscience Letters. 461 (1): 54–9. doi:10.1016/j.neulet.2009.05.051. PMID   19477230. S2CID   9038729.
  27. ↑ Buffo A, Vosko MR, Ertürk D, Hamann GF, Jucker M, Rowitch D, Götz M (Dec 2005). "Expression pattern of the transcription factor Olig2 in response to brain injuries: implications for neuronal repair". Proceedings of the National Academy of Sciences of the United States of America. 102 (50): 18183–8. Bibcode:2005PNAS..10218183B. doi: 10.1073/pnas.0506535102 . PMC   1312388 . PMID   16330768.
  28. ↑ Buffo A, Rite I, Tripathi P, Lepier A, Colak D, Horn AP, Mori T, Götz M (Mar 2008). "Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain". Proceedings of the National Academy of Sciences of the United States of America. 105 (9): 3581–6. Bibcode:2008PNAS..105.3581B. doi: 10.1073/pnas.0709002105 . PMC   2265175 . PMID   18299565.

Further reading

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