Nurr1, an orphan nuclear receptor with essential functions in developing dopamine cells

Cell and Tissue Research

Volumn 318, Issue 1, 2004, Pages 45-52

  Perlmann, Thomas ^a,b   Wallén Mackenzie, Åsa ^a  

^a Ludwig Institute   (Sweden)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Dopamine cell development; NR4A2; Nuclear receptor; Nurr1; Orphan receptor; Parkinson's disease; Transcription factor

Indexed keywords

AMINO ACID DECARBOXYLASE; CELL NUCLEUS RECEPTOR; CORTICOTROPIN RELEASING FACTOR; DOPAMINE; FIBROBLAST GROWTH FACTOR 8; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; LIGAND; MESSENGER RNA; NEUROTOXIN; NUCLEAR RECEPTOR RELATED FACTOR 1; OXIDOPAMINE; PROTEIN P57; PROTEIN TYROSINE KINASE; RETINOID X RECEPTOR; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR; TYROSINE 3 MONOOXYGENASE;

CELL SURVIVAL; CLINICAL TRIAL; DEVELOPMENT; DOPAMINERGIC NERVE CELL; GENE EXPRESSION; HUMAN; MESENCEPHALON; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; STEM CELL; SUBSTANTIA NIGRA; TISSUE TRANSPLANTATION; VENTRAL TEGMENTUM;

ANIMALS; DNA-BINDING PROTEINS; DOPAMINE; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HUMANS; MESENCEPHALON; NEURONS; TRANSCRIPTION FACTORS;

ERINACEIDAE;

EID: 5544325468     PISSN: 0302766X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00441-004-0974-7     Document Type: Review

References (77)

1. Arkenbout EK, Waard V de, Bragt M van, Achterberg TA van, Grimbergen JM, Pichon B, Pannekoek H, Vries CJ de (2002) Protective function of transcription factor TR3 orphan receptor in atherogenesis: decreased lesion formation in carotid artery ligation model in TR3 transgenic mice. Circulation 106:1530-1535
2. Arkenbout EK, Bragt M van, Eldering E, Bree C van, Grimbergen JM, Quax PH, Pannekoek H, Vries CJ de (2003) TR3 orphan receptor is expressed in vascular endothelial cells and mediates cell cycle arrest. Arterioscler Thromb Vasc Biol 23:1535-1540
3. Backman C, Perlmann T, Wallén Å, Hoffer BJ, Morales M (1999) A selective group of dopaminergic neurons express Nurr1 in the adult mouse brain. Brain Res 851:125-132
4. Backman C, You ZB, Perlmann T, Hoffer BJ (2003) Elevated locomotor activity without altered striatal dopamine contents in Nurr1 heterozygous mice after acute exposure to methamphetamine. Behav Brain Res 143:95-100
5. Bassett MH, Suzuki T, Sasano H, White PC, Rainey WE (2004) The orphan nuclear receptors NURR1 and NGFIB regulate adrenal aldosterone production. Mol Endocrinol 18:279-290
6. Buervenich S, Carmine A, Arvidsson M, Xiang F, Zhang Z, Sydow O, Jonsson EG, Sedvall GC, Leonard S, Ross RG, Freedman R, Chowdari KV, Nimgaonkar VL, Perlmann T, Anvret M, Olson L (2000) NURR1 mutations in cases of schizophrenia and manic-depressive disorder. Am J Med Genet 96:808-813
7. Castillo SO, Baffi JS, Palkovits M, Goldstein DS, Kopin IJ, Witta J, Magnuson MA, Nikodem VM (1998) Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disruption of the Nurr1 gene. Mol Cell Neurosci 11:36-46
8. Castro DS, Hermanson E, Joseph B, Wallén Å, Aarnisalo P, Heller A, Perlmann T (2001) Induction of cell cycle arrest and morphological differentiation by Nurr1 and retinoids in dopamine MN9D cells. J Biol Chem 276:43277-43284
9. Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ (2001) Nuclear receptors and lipid physiology: opening the X-files. Science 294:1866-1870
10. Chu Y, Kompoliti K, Cochran EJ, Mufson EJ, Kordower JH (2002) Age-related decreases in Nurr1 immunoreactivity in the human substantia nigra. J Comp Neurol 450:203-214
11. Chung S, Sonntag KC, Andersson T, Bjorklund LM, Park JJ, Kim DW, Kang UJ, Isacson O, Kim KS (2002) Genetic engineering of mouse embryonic stem cells by Nurr1 enhances differentiation and maturation into dopaminergic neurons. Eur J Neurosci 16:1829-1838
12. Crispino M, Tocco G, Feldman JD, Herschman HR, Baudry M (1998) Nurr1 mRNA expression in neonatal and adult rat brain following kainic acid-induced seizure activity. Brain Res Mol Brain Res 59:178-188
13. Dunnett SB, Bjorklund A, Lindvall O (2001) Cell therapy in Parkinson's disease - stop or go? Nat Rev Neurosci 2:365-369
14. Eells JB, Lipska BK, Yeung SK, Misler JA, Nikodem VM (2002) Nurr1-null heterozygous mice have reduced mesolimbic and mesocortical dopamine levels and increased stress-induced locomotor activity. Behav Brain Res 136:267-275
15. Falck B, Hillarp N-Å, Thieme G, Torp A (1962) Fluorescence of catechol amines and related compounds condensed with formaldehyde. J Histochem Cytochem 10:348-354
16. Granholm AC, Reyland M, Albeck D, Sanders L, Gerhardt G, Hoernig G, Shen L, Westphal H, Hoffer B (2000) Glial cell line-derived neurotrophic factor is essential for postnatal survival of midbrain dopamine neurons. J Neurosci 20:3182-3190
17. Hering R, Petrovic S, Mietz EM, Holzmann C, Berg D, Bauer P, Woitalla D, Muller T, Berger K, Kruger R, Riess O (2004) Extended mutation analysis and association studies of Nurr1 (NR4A2) in Parkinson disease. Neurology 62:1231-1232
18. Hermanson E, Joseph B, Castro D, Lindqvist E, Aarnisalo P, Wallén Å, Benoit G, Hengerer B, Olson L, Perlmann T (2003) Nurr1 regulates dopamine synthesis and storage in MN9D dopamine cells. Exp Cell Res 288:324-334
19. Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C (1992) 9-cis Retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 68:397-406
20. Honkaniemi J, Sharp FR (1996) Global ischemia induces immediate-early genes encoding zinc finger transcription factors. J Cereb Blood Flow Metab 16:557-565
21. Honkaniemi J, Sharp FR (1999) Prolonged expression of zinc finger immediate-early gene mRNAs and decreased protein synthesis following kainic acid induced seizures. Eur J Neurosci 11:10-17
22. Honkaniemi J, Sagar SM, Pyykonen I, Hicks KJ, Sharp FR (1995) Focal brain injury induces multiple immediate early genes encoding zinc ringer transcription factors. Brain Res Mol Brain Res 28:157-163
23. Honkaniemi J, States BA, Weinstein PR, Espinoza J, Sharp FR (1997) Expression of zinc finger immediate early genes in rat brain after permanent middle cerebral artery occlusion. J Cereb Blood Flow Metab 17:636-646
24. Hynes M, Rosenthal A (1999) Specification of dopaminergic and serotonergic neurons in the vertebrate CNS. Curr Opin Neurobiol 9:26-36
25. Hynes M, Porter JA, Chiang C, Chang D, Tessier-Lavigne M, Beachy PA, Rosenthal A (1995) Induction of midbrain dopaminergic neurons by sonic hedgehog. Neuron 15:33-44
26. Iwawaki T, Kohno K, Kobayashi K (2000) Identification of a potential Nurr1 response element that activates the tyrosine hydroxylase gene promoter in cultured cells. Biochem Biophys Res Commun 274:590-595
27. Joseph B, Wallén-Mackenzie Å, Benoit G, Murata T, Joodmardi E, Okret S, Perlmann T (2003) p57(Kip2) cooperates with Nurr1 in developing dopamine cells. Proc Natl Acad Sci USA 100:15619-15624
28. Kim JH, Auerbach JM, Rodriguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, Lee SH, Nguyen J, Sanchez-Pernuaute R, Bankiewicz K, McKay R (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 418:50-56
29. Kim KS, Kim CH, Hwang DY, Seo H, Chung S, Hong SJ, Lim JK, Anderson T, Isacson O (2003a) Orphan nuclear receptor Nurr1 directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell-specific manner. J Neurochem 85:622-634
30. Kim TE, Lee HS, Lee YB, Hong SH, Lee YS, Ichinose H, Kim SU, Lee MA (2003b) Sonic hedgehog and FGF8 collaborate to induce dopaminergic phenptypes in the Nurr1-overexpressing neural stem cell. Biochem Biophys Res Commun 305:1040-1048
31. Kliewer SA, Lehmann JM, Willson TM (1999) Orphan nuclear receptors: shifting endocrinology into reverse. Science 284:757-760
32. Lammi J, Huppunen J, Aarnisalo P (2004) Regulation of the osteopontin gene by the orphan nuclear receptor Nurr1 in osteoblasts. Mol Endocrinol 18:1546-1557
33. Law SW, Conneely OM, DeMayo FJ, O'Malley BW (1992) Identification of a new brain-specific transcription factor, NURR1. Mol Endocrinol 6:2129-2135
34. Le W, Conneely OM, He Y, Jankovic J, Appel SH (1999a) Reduced Nurr1 expression increases the vulnerability of mesencephalic dopamine neurons to MPTP-induced injury. J Neurochem 73:2218-2221
35. Le W, Conneely OM, Zou L, He Y, Saucedo-Cardenas O, Jankovic J, Mosier DR, Appel SH (1999b) Selective agenesis of mesencephalic dopaminergic neurons in Nurr1-deficient mice. Exp Neurol 159:451-458
36. Le WD, Xu P, Jankovic J, Jiang H, Appel SH, Smith RG, Vassilatis DK (2003) Mutations in NR4A2 associated with familial Parkinson disease. Nat Genet 33:85-89
37. Liu D, Jia H, Holmes DI, Stannard A, Zachary I (2003) Vascular endothelial growth factor-regulated gene expression in endothelial cells: KDR-mediated induction of Egr3 and the related nuclear receptors Nur77, Nurr1, and Nor1. Arterioscler Thromb Vasc Biol 23:2002-2007
38. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, et al (1995) The nuclear receptor superfamily: the second decade. Cell 83:835-839
39. Mata de Urquiza A, Liu S, Sjöberg M, Zetterström RH, Griffiths W, Sjövall J, Perlmann T (2000) Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 290:2140-2144
40. McEvoy AN, Bresnihan B, Fitzgerald O, Murphy EP (2002) Corticotropin-releasing hormone signaling in synovial tissue vascular endothelium is mediated through the cAMP/CREB pathway. Ann N Y Acad Sci 966:119-130
41. Murphy EP, McEvoy A, Conneely OM, Bresnihan B, FitzGerald O (2001) Involvement of the nuclear orphan receptor NURR1 in the regulation of corticotropin-releasing hormone expression and actions in human inflammatory arthritis. Arthritis Rheum 44:782-793
42. Nsegbe E, Wallén-Mackenzie Å, Dauger S, Roux JC, Shvarev Y, Lagercrantz H, Perlmann T, Herlenius E (2004) Congenital hypoventilation and impaired hypoxic response in Nurr1 mutant mice. J Physiol (Lond) 556:43-59
43. Ojeda V, Fuentealba JA, Galleguillos D, Andres ME (2003) Rapid increase of Nurr1 expression in the substantia nigra after 6-hydroxydopamine lesion in the striatum of the rat. J Neurosci Res 73:686-697
44. Oo TF, Kholodilov N, Burke RE (2003) Regulation of natural cell death in dopaminergic neurons of the substantia nigra by striatal glial cell line-derived neurotrophic factor in vivo. J Neurosci 23:5141-5148
45. Ordentlich P, Yan Y, Zhou S, Heyman RA (2003) Identification of the anti-neoplastic agent 6-mercaptopurine as an activator of the orphan nuclear hormone receptor Nurr1. J Biol Chem 22:22
46. Pena de Ortiz S, Jamieson GAJ (1996) GAJ HZF-3, an immediate-early orphan receptor homologous to Nurr1/NOT: induction upon membrane depolarization and seizures. Brain Res Mol Brain Res 38:1-13
47. Perlmann T, Jansson L (1995) A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1. Genes Dev 9:769-782
48. Philips A, Lesage S, Gingras R, Maira MH, Gauthier Y, Hugo P, Drouin J (1997) Novel dimeric Nur77 signaling mechanism in endocrine and lymphoid cells. Mol Cell Biol 17:5946-5951
49. Riddle R, Pollock JD (2003) Making connections: the development of mesencephalic dopaminergic neurons. Dev Brain Res 147:3-21
50. Sacchetti P, Brownschidle LA, Granneman JG, Bannon MJ (1999) Characterization of the 5′-flanking region of the human dopamine transporter gene. Brain Res Mol Brain Res 74:167-174
51. Sacchetti P, Mitchell TR, Granneman JG, Bannon MJ (2001) Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism. J Neurochem 76:1565-1572
52. Sakurada K, Ohshima-Sakurada M, Palmer TD, Gage FH (1999) Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain. Development 126:4017-4026
53. Saucedo-Cardenas O, Conneely OM (1996) Comparative distribution of NURR1 and NUR77 nuclear receptors in the mouse central nervous system. J Mol Neurosci 7:51-63
54. Saucedo-Cardenas O, Quintana-Hau JD, Le WD, Smidt MP, Cox JJ, De Mayo F, Burbach JP, Conneely OM (1998) Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc Natl Acad Sci USA 95:4013-4018
55. Scearce LM, Laz TM, Hazel TG, Lau LF, Taub R (1993) RNR-1, a nuclear receptor in the NGFI-B/Nur77 family that is rapidly induced in regenerating liver. J Biol Chem 268:8855-8861
56. Simon HH, Saueressig H, Wurst W, Goulding MG, O'Leary DD (1998) En-1 and En-2 control the fate of the dopaminergic neurons in the substantia nigra and ventral tegmentum. Eur J Neurosci 10(Suppl 10):389
57. Smidt MP, Schaick HS van, Lanctot C, Tremblay JJ, Cox JJ, Kleij AA van der, Wolterink G, Drouin J, Burbach JP (1997) A homeodomain gene Ptx3 has highly restricted brain expression in mesencephalic dopaminergic neurons. Proc Natl Acad Sci USA 94:13305-13310
58. Smidt MP, Asbreuk CH, Cox JJ, Chen H, Johnson RL, Burbach JP (2000) A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b. Nat Neurosci 3:337-341
59. Smits SM, Ponnio T, Conneely OM, Burbach JP, Smidt MP (2003) Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic neurons. Eur J Neurosci 18:1731-1738
60. Sonntag KC, Simantov R, Kim KS, Isacson O (2004) Temporally induced Nurr1 can induce a non-neuronal dopaminergic cell type in embryonic stem cell differentiation. Eur J Neurosci 19:1141-1152
61. Tan EK, Chung H, Zhao Y, Shen H, Chandran VR, Tan C, Teoh ML, Yih Y, Pavanni R, Wong MC (2003) Genetic analysis of Nurr1 haplotypes in Parkinson's disease. Neurosci Lett 347:139-142
62. Thuret S, Bhatt L, O'Leary DD, Simon HH (2004) Identification and developmental analysis of genes expressed by dopaminergic neurons of the substantia nigra pars compacta. Mol Cell Neurosci 25:394-405
63. Tseng KY, Roubert C, Do L, Rubinstein M, Kelly MA, Grandy DK, Low MJ, Gershanik OS, Murer MG, Giros B, Raisman-Vozari R (2000) Selective increase of Nurr1 mRNA expression in mesencephalic dopaminergic neurons of D2 dopamine receptor-deficient mice. Brain Res Mol Brain Res 80:1-6
64. Ungerstedt U (1971) Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol Scand Suppl 367:1-48
65. Wagner J, Akerud P, Castro DS, Holm PC, Canals JM, Snyder EY, Perlmann T, Arenas E (1999) Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes. Nat Biotechnol 17:653-659
66. Wallén Å, Zetterstrom RH, Solomin L, Arvidsson M, Olson L, Perlmann T (1999) Fate of mesencephalic AHD2-expressing dopamine progenitor cells in NURR1 mutant mice. Exp Cell Res 253:737-746
67. Wallén Å, Castro DS, Zetterström RH, Karlén M, Olson L, Ericson J, Perlmann T (2001) Orphan nuclear receptor Nurr1 is essential for Ret expression in the midbrain dopamine neurons and in the brain stem. Mol Cell Neurosci 18:649-663
68. Wallén-Mackenzie Å, Mata de Urquiza A, Petersson S, Rodriguez FJ, Friling S, Wagner J, Ordentlich P, Lengqvist J, Heyman RA, Arenas E, Perlmann T (2003) Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells. Genes Dev 17:3036-3047
69. Wang Z, Benoit G, Liu J, Prasad S, Aarnisalo P, Liu X, Xu H, Walker NP, Perlmann T (2003) Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors. Nature 423:555-560
70. Werme M, Hermanson E, Carmine A, Buervenich S, Zetterstrom RH, Thoren P, Ogren SO, Olson L, Perlmann T, Brene S (2003) Decreased ethanol preference and wheel running in Nurr1-deficient mice. Eur J Neurosci 17:2418-2424
71. Witta J, Baffi JS, Palkovits M, Mezey E, Castillo SO, Nikodem VM (2000) Nigrostriatal innervation is preserved in Nurr1-null mice, although dopaminergic neuron precursors are arrested from terminal differentiation. Brain Res Mol Brain Res 84:67-78
72. Wurst W, Bally-Cuif L (2001) Neural plate patterning: upstream and downstream of the isthmic organizer. Nat Rev Neurosci 2:99-108
73. Xing G, Zhang L, Heynen T, Li XL, Smith MA, Weiss SR, Feldman AN, Detera-Wadleigh S, Chuang DM, Post RM (1997) Rat Nurr1 is prominently expressed in perirhinal cortex, and differentially induced in the hippocampal dentate gyrus by electroconvulsive vs. kindled seizures. Brain Res Mol Brain Res 47:251-261
74. Zetterstrom RH, Solomin L, Mitsiadis T, Olson L, Perlmann T (1996a) Retinoid X receptor heterodimerization and developmental expression distinguish the orphan nuclear receptors NGFI-B, Nurr1, and Nor1. Mol Endocrinol 10:1656-1666
75. Zetterström RH, Williams R, Perlmann T, Olson L (1996b) Cellular expression of the immediate early transcription factors Nurr1 and NGFI-B suggests a gene regulatory role in several brain regions including the nigrostriatal dopamine system. Brain Res Mol Brain Res 41:111-120
76. Zetterström RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T (1997) Dopamine neuron agenesis in Nurr1-deficient mice. Science 276:248-250
77. Zhou QY, Palmiter RD (1995) Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell 83:1197-1209