Home LiteratureArticle Details
PMID: 9889200 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A role for the POU-III transcription factor Brn-4 in the regulation of striatal neuron precursor differentiation.

The EMBO journal ·Vol. 18 ·No. 2 ·1999-01-15 ·Pages 444-56

Shimazaki T, Arsenijevic Y, Ryan AK, Rosenfeld MG, Weiss S

Abstract

Both insulin-like growth factor-I (IGF-I) and brain-derived neurotrophic factor (BDNF) induce the differentiation of post-mitotic neuronal precursors, derived from embryonic day 14 (E14) mouse striatal multipotent stem cells. Here we ask whether this differentiation is mediated by a member of the POU-III class of neural transcription factors. Exposure of stem cell progeny to either IGF-I or BDNF resulted in a rapid upregulation of Brn-4 mRNA and protein. Indirect immunocytochemistry with Brn-4 antiserum showed that the protein was expressed in newly generated neurons. Other POU-III genes, such as Brn-1 and Brn-2, did not exhibit this upregulation. Basic FGF, a mitogen for these neuronal precursors, did not stimulate Brn-4 expression. In the E14 mouse striatum, Brn-4-immunoreactive cells formed a boundary between the nestin-immunoreactive cells of the ventricular zone and the beta-tubulin-immunoreactive neurons migrating into the mantle zone. Loss of Brn-4 function during the differentiation of stem cell-derived or primary E14 striatal neuron precursors, by inclusion of antisense oligonucleotides, caused a reduction in the number of beta-tubulin-immunoreactive neurons. These findings suggest that Brn-4 mediates, at least in part, the actions of epigenetic signals that induce striatal neuron-precursor differentiation.

MeSH Terms
Animals Base Sequence Brain-Derived Neurotrophic Factor/pharmacology Cell Differentiation/drug effects Corpus Striatum/cytology,metabolism DNA Primers/genetics DNA, Antisense/genetics,pharmacology DNA-Binding Proteins In Vitro Techniques Insulin-Like Growth Factor I/pharmacology Mice Nerve Tissue Proteins Neurons/cytology,drug effects,metabolism POU Domain Factors Stem Cells/cytology,drug effects,metabolism Transcription Factors/genetics,metabolism
Chemicals
Brain-Derived Neurotrophic Factor DNA Primers DNA, Antisense DNA-Binding Proteins Nerve Tissue Proteins POU Domain Factors Transcription Factors Pou3f4 protein, mouse Insulin-Like Growth Factor I
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shimazaki T
Department of Cell Biology and Anatomy, University of Calgary Faculty of Medicine, 3330 Hospital Drive N.W., Calgary, AB, Canada T2N 4N1.
Arsenijevic Y
Ryan A K
Rosenfeld M G
Weiss S
References (74)
74 references, click to expand
  1. Cellular pattern of type-I insulin-like growth factor receptor gene expression during maturation of the rat brain: comparison with insulin-like growth factors I and II.
    Neuroscience. 1992;46(4):909-23 PMID: 1311816
  2. Expression of IGF-1 mRNA in the murine subventricular zone during postnatal development.
    Brain Res Mol Brain Res. 1992 Feb;12(4):285-91 PMID: 1315903
  3. RHS2, a POU domain-containing gene, and its expression in developing and adult rat.
    Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3285-9 PMID: 1348858
  4. A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes.
    J Neurosci. 1992 Nov;12(11):4565-74 PMID: 1432110
  5. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.
    Science. 1992 Mar 27;255(5052):1707-10 PMID: 1553558
  6. Structure and evolution of four POU domain genes expressed in mouse brain.
    Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3280-4 PMID: 1565620
  7. Therapeutic applications of oligonucleotides.
    Annu Rev Pharmacol Toxicol. 1992;32:329-76 PMID: 1605571
  8. Brain 4: a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression.
    EMBO J. 1992 Jul;11(7):2551-61 PMID: 1628619
  9. The regulation of transcription by phosphorylation.
    Cell. 1992 Aug 7;70(3):375-87 PMID: 1643656
  10. Expression of IGF-I and insulin receptor genes in the rat central nervous system: a developmental, regional, and cellular analysis.
    J Neurosci Res. 1991 Feb;28(2):244-53 PMID: 1851850
  11. Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1.
    Nature. 1990 Oct 11;347(6293):528-33 PMID: 1977085
  12. Regional expression of the nerve growth factor gene family in rat brain during development.
    Biochem Biophys Res Commun. 1991 Jan 15;174(1):379-85 PMID: 1989616
  13. Quantitative estimation of minor mRNAs by cDNA-polymerase chain reaction. Application to dystrophin mRNA in cultured myogenic and brain cells.
    Eur J Biochem. 1990 Feb 14;187(3):691-8 PMID: 2406139
  14. A human protein specific for the immunoglobulin octamer DNA motif contains a functional homeobox domain.
    Cell. 1988 Oct 7;55(1):135-44 PMID: 2901913
  15. The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein.
    Cell. 1988 Nov 4;55(3):505-18 PMID: 2902927
  16. A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype.
    Cell. 1988 Nov 4;55(3):519-29 PMID: 2902928
  17. The C. elegans cell lineage and differentiation gene unc-86 encodes a protein with a homeodomain and extended similarity to transcription factors.
    Cell. 1988 Dec 2;55(5):757-69 PMID: 2903797
  18. A human lymphoid-specific transcription factor that activates immunoglobulin genes is a homoeobox protein.
    Nature. 1988 Dec 8;336(6199):551-7 PMID: 2904654
  19. O-glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation.
    Cell. 1988 Oct 7;55(1):125-33 PMID: 3139301
  20. The B-cell-specific Oct-2 protein contains POU box- and homeo box-type domains.
    Genes Dev. 1988 Dec;2(12A):1570-81 PMID: 3265124
  21. Nucleotide sequence of a full-length cDNA for mouse cytoskeletal beta-actin mRNA.
    Nucleic Acids Res. 1986 Mar 25;14(6):2829 PMID: 3754329
  22. Sequences of liver cDNAs encoding two different mouse insulin-like growth factor I precursors.
    Nucleic Acids Res. 1986 Oct 24;14(20):7873-82 PMID: 3774549
  23. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo.
    J Biol Chem. 1995 Nov 17;270(46):27489-94 PMID: 7499206
  24. Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells.
    J Biol Chem. 1993 Dec 5;268(34):25846-56 PMID: 7503989
  25. Neurotrophin signalling.
    Curr Opin Neurobiol. 1994 Oct;4(5):668-79 PMID: 7531524
  26. Characterization of TrkB receptor-mediated signaling pathways in rat cerebellar granule neurons: involvement of protein kinase C in neuronal survival.
    J Neurochem. 1995 Nov;65(5):2241-50 PMID: 7595513
  27. Model of forebrain regionalization based on spatiotemporal patterns of POU-III homeobox gene expression, birthdates, and morphological features.
    J Comp Neurol. 1995 May 1;355(2):237-95 PMID: 7608343
  28. BDNF enhances the differentiation but not the survival of CNS stem cell-derived neuronal precursors.
    J Neurosci. 1995 Aug;15(8):5765-78 PMID: 7643217
  29. A synthetic inhibitor of the mitogen-activated protein kinase cascade.
    Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7686-9 PMID: 7644477
  30. Nestin mRNA expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system.
    Brain Res Dev Brain Res. 1995 Jan 14;84(1):109-29 PMID: 7720210
  31. XIPOU 2, a noggin-inducible gene, has direct neuralizing activity.
    Development. 1995 Mar;121(3):721-30 PMID: 7720579
  32. Nerve growth factor induces the Oct-2 transcription factor in sensory neurons with the kinetics of an immediate-early gene.
    J Neurosci Res. 1995 Feb 1;40(2):169-76 PMID: 7745610
  33. The developing CNS: a scenario for the action of proinsulin, insulin and insulin-like growth factors.
    Trends Neurosci. 1995 Mar;18(3):143-50 PMID: 7754526
  34. Regulation of neurite outgrowth and SNAP-25 gene expression by the Brn-3a transcription factor.
    J Biol Chem. 1995 Jun 30;270(26):15858-63 PMID: 7797590
  35. Antisense oligodeoxynucleotides.
    Curr Opin Oncol. 1994 Nov;6(6):587-94 PMID: 7827170
  36. Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.
    Science. 1995 Feb 3;267(5198):685-8 PMID: 7839145
  37. Regulation of the POU domain gene SCIP during cerebral cortical development.
    J Neurosci. 1994 Feb;14(2):472-85 PMID: 7905511
  38. Expression of neuron-specific tubulin defines a novel population in the proliferative layers of the developing telencephalon.
    J Neurosci. 1994 Sep;14(9):5399-416 PMID: 8083744
  39. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002).
    J Biol Chem. 1994 Feb 18;269(7):5241-8 PMID: 8106507
  40. Differential induction of Pax genes by NGF and BDNF in cerebellar primary cultures.
    J Cell Biol. 1994 Apr;125(2):417-25 PMID: 8163557
  41. bFGF regulates the proliferative fate of unipotent (neuronal) and bipotent (neuronal/astroglial) EGF-generated CNS progenitor cells.
    Neuron. 1993 Nov;11(5):951-66 PMID: 8240816
  42. Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses.
    Biochem J. 1993 Dec 1;296 ( Pt 2):297-301 PMID: 8257416
  43. A CNS-specific POU transcription factor, Brn-2, is required for establishing mammalian neural cell lineages.
    Neuron. 1993 Dec;11(6):1197-206 PMID: 8274283
  44. Spacing and orientation of bipartite DNA-binding motifs as potential functional determinants for POU domain factors.
    Genes Dev. 1993 Dec;7(12B):2483-96 PMID: 8276233
  45. Signal transduction events mediated by the BDNF receptor gp 145trkB in primary hippocampal pyramidal cell culture.
    J Neurosci. 1993 Oct;13(10):4281-92 PMID: 8410187
  46. The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse.
    Genes Dev. 1995 Dec 15;9(24):3109-21 PMID: 8543155
  47. Development and survival of the endocrine hypothalamus and posterior pituitary gland requires the neuronal POU domain factor Brn-2.
    Genes Dev. 1995 Dec 15;9(24):3122-35 PMID: 8543156
  48. Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell.
    Dev Biol. 1996 Apr 10;175(1):1-13 PMID: 8608856
  49. POU domain factor Brn-3b is required for the development of a large set of retinal ganglion cells.
    Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3920-5 PMID: 8632990
  50. Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development.
    Nature. 1996 Jun 13;381(6583):603-6 PMID: 8637595
  51. Phosphorothioate antisense oligodeoxynucleotides: questions of specificity.
    Trends Biotechnol. 1996 May;14(5):147-9 PMID: 8645447
  52. The POU factor Oct-6 and Schwann cell differentiation.
    Science. 1996 Jul 26;273(5274):507-10 PMID: 8662541
  53. Tst-1/Oct-6/SCIP regulates a unique step in peripheral myelination and is required for normal respiration.
    Genes Dev. 1996 Jul 15;10(14):1751-62 PMID: 8698235
  54. Progress in antisense oligonucleotide therapeutics.
    Annu Rev Pharmacol Toxicol. 1996;36:107-29 PMID: 8725384
  55. Binding preferences of the POU domain protein Brain-4: implications for autoregulation.
    Brain Res Mol Brain Res. 1996 Jun;38(2):209-21 PMID: 8793109
  56. Intracellular signaling pathways activated by neurotrophic factors.
    Annu Rev Neurosci. 1996;19:463-89 PMID: 8833451
  57. Development of striatal dopaminergic function. III: Pre- and postnatal development of striatal and cortical mRNAs for the neurotrophin receptors trkBTK+ and trkC and their regulation by synaptic dopamine.
    Brain Res Dev Brain Res. 1996 Jul 20;94(2):133-43 PMID: 8836571
  58. Identification of a hot spot for microdeletions in patients with X-linked deafness type 3 (DFN3) 900 kb proximal to the DFN3 gene POU3F4.
    Hum Mol Genet. 1996 Sep;5(9):1229-35 PMID: 8872461
  59. Is there a neural stem cell in the mammalian forebrain?
    Trends Neurosci. 1996 Sep;19(9):387-93 PMID: 8873356
  60. Targeted deletion of the mouse POU domain gene Brn-3a causes selective loss of neurons in the brainstem and trigeminal ganglion, uncoordinated limb movement, and impaired suckling.
    Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11950-5 PMID: 8876243
  61. Developmental and mature expression of full-length and truncated TrkB receptors in the rat forebrain.
    J Comp Neurol. 1996 Oct 7;374(1):21-40 PMID: 8891944
  62. Patterning the vertebrate neuraxis.
    Science. 1996 Nov 15;274(5290):1109-15 PMID: 8895453
  63. Requirement for Brn-3.0 in differentiation and survival of sensory and motor neurons.
    Nature. 1996 Dec 12;384(6609):574-7 PMID: 8955272
  64. Insulin-like growth factor 1 inhibits apoptosis using the phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways.
    J Biol Chem. 1997 Jan 3;272(1):154-61 PMID: 8995241
  65. Regulation of neuronal survival by the serine-threonine protein kinase Akt.
    Science. 1997 Jan 31;275(5300):661-5 PMID: 9005851
  66. Insulin-like growth factor and potassium depolarization maintain neuronal survival by distinct pathways: possible involvement of PI 3-kinase in IGF-1 signaling.
    J Neurosci. 1997 Mar 1;17(5):1548-60 PMID: 9030615
  67. Signal transduction by the neurotrophin receptors.
    Curr Opin Cell Biol. 1997 Apr;9(2):213-21 PMID: 9069267
  68. POU domain family values: flexibility, partnerships, and developmental codes.
    Genes Dev. 1997 May 15;11(10):1207-25 PMID: 9171367
  69. Mutations of the homeobox genes Dlx-1 and Dlx-2 disrupt the striatal subventricular zone and differentiation of late born striatal neurons.
    Neuron. 1997 Jul;19(1):27-37 PMID: 9247261
  70. Redundancy of class III POU proteins in the oligodendrocyte lineage.
    J Biol Chem. 1997 Dec 19;272(51):32286-93 PMID: 9405434
  71. Insulin-like growth factor-I is a differentiation factor for postmitotic CNS stem cell-derived neuronal precursors: distinct actions from those of brain-derived neurotrophic factor.
    J Neurosci. 1998 Mar 15;18(6):2118-28 PMID: 9482798
  72. NT-3 regulates expression of Brn3a but not Brn3b in developing mouse trigeminal sensory neurons.
    Brain Res Mol Brain Res. 1998 Apr;55(2):254-64 PMID: 9582431
  73. Requirement for Brn-3b in early differentiation of postmitotic retinal ganglion cell precursors.
    Dev Biol. 1998 May 15;197(2):155-69 PMID: 9630743
  74. Bcl-2 transcription from the proximal P2 promoter is activated in neuronal cells by the Brn-3a POU family transcription factor.
    J Biol Chem. 1998 Jul 3;273(27):16715-22 PMID: 9642226
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/18.2.444
Published
1999-01-15
Pages
444-56
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171138
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/18.2.444 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2