Skip to main content

Advertisement

SpringerLink
Log in

Nuclear receptors in neural stem/progenitor cell homeostasis

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

In the central nervous system, embryonic and adult neural stem/progenitor cells (NSCs) generate the enormous variety and huge numbers of neuronal and glial cells that provide structural and functional support in the brain and spinal cord. Over the last decades, nuclear receptors and their natural ligands have emerged as critical regulators of NSC homeostasis during embryonic development and adult life. Furthermore, substantial progress has been achieved towards elucidating the molecular mechanisms of nuclear receptors action in proliferative and differentiation capacities of NSCs. Aberrant expression or function of nuclear receptors in NSCs also contributes to the pathogenesis of various nervous system diseases. Here, we review recent advances in our understanding of the regulatory roles of steroid, non-steroid, and orphan nuclear receptors in NSC fate decisions. These studies establish nuclear receptors as key therapeutic targets in brain diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

AADC:

Aromatic l-amino acid decarboxylase

Aβ:

Amyloid beta

AD:

Alzheimer’s disease

AGE:

Advanced glycated end

ALS:

Amyotrophic lateral sclerosis

APP:

Amyloid precursor protein

BBB:

Blood-brain barrier

BDNF:

Brain-derived neurotrophic factor

BPA:

Bisphenol A

Bxt:

Bexarotene

CA:

3α,7α,12α-Trihydroxy-5β-cholan-24-oic acid

CNS:

Central nervous system

CNTF:

Ciliary neurotrophic factor

COUP-TF:

Chicken ovalbumin upstream promoter-transcription factor

DA:

Dopaminergic

DAT:

Dopamine transporter

DBD:

DNA binding domain

DEX:

Dexamethasone

DG:

Dentate gyrus

DHA:

Docosahexaenoic acid

DVD:

Developmental vitamin D

E2:

17β-Estradiol

ER:

Estrogen receptor

ERE:

Estrogen response element

ESCs:

Embryonic stem cells

Ftz-F1:

Fushi tarazu factor 1

GC:

Glucocorticoid

GCNF:

Germ cell nuclear factor

GDNF:

Glial-derived neurotrophic factor

GJIC:

Gap junction intracellular communication

GR:

Glucocorticoid receptor

GRE:

Glucocorticoid response element

HDAC:

Histone deacetylase

HPA:

Hypothalamus–pituitary–adrenals

iPSCs:

Induced pluripotent stem cells

LBD:

Ligand-binding domain

LRH-1:

Liver receptor homolog 1

LXR:

Liver X receptor

MAP2:

Microtubule-associated protein 2

MR:

Minerolocorticoid receptor

MSCs:

Mesenchymal stem cells

NBRE:

NGFI-B response element

N-CoR:

Nuclear receptor co-repressor

NGF:

Nerve growth factor

NLS:

Nuclear localization signal

NR:

Nuclear receptor

NSCs:

Neural stem/progenitor cells

NT-3:

Neurotrophin-3

Nurr1:

Nuclear receptor-related 1 protein

PD:

Parkinson’s disease

Pex11β:

Peroxisomal membrane elongation factor

Pitx3:

Pituitary homeobox 3

PPAR:

Peroxisome-proliferator-activated receptor

PPRE:

Peroxisome-proliferator DNA response element

PRMT1:

Protein arginine methyl transferase 1

PRMT8:

Protein arginine methyl transferase 8

RA:

Retinoic acid

RAR:

Retinoic acid receptor

RARE:

Retinoic acid response element

RXR:

Retinoic X receptor

SF-1:

Steroidogenic factor 1

SGZ:

Subgranular zone

Shh:

Sonic hedgehog

SVZ:

Subventricular zone

Syp:

Synaptic vesicle protein synaptophysin

T3:

3,5,39-Triiodo-l-thyronine

T4:

3,5,39,59-Tetraiodo-l-thyronine

TH:

Tyrosine hydroxylase

TR:

Thyroid hormone receptor

TRE:

Thyroid hormone response element

VDR:

Vitamin D receptor

VDRE:

VDR response element

VMAT2:

Vesicular monoamine transporter-2

VMH:

Ventromedial hypothalamic

VMN:

Ventromedial hypothalamic nucleus

References

  1. Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124(3):319–335

    Article  CAS  PubMed  Google Scholar 

  2. Eriksson PS et al (1998) Neurogenesis in the adult human hippocampus. Nat Med 4(11):1313–1317

    Article  CAS  PubMed  Google Scholar 

  3. Spalding KL et al (2013) Dynamics of hippocampal neurogenesis in adult humans. Cell 153(6):1219–1227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bond AM, Ming GL, Song H (2015) Adult mammalian neural stem cells and neurogenesis: five decades later. Cell Stem Cell 17(4):385–395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Schulman IG (2010) Nuclear receptors as drug targets for metabolic disease. Adv Drug Deliv Rev 62(13):1307–1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Overington JP, Al-Lazikani B, Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5(12):993–996

    Article  CAS  PubMed  Google Scholar 

  7. Moore JT, Collins JL, Pearce KH (2006) The nuclear receptor superfamily and drug discovery. ChemMedChem 1(5):504–523

    Article  CAS  PubMed  Google Scholar 

  8. Anacker C et al (2011) Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor. Mol Psychiatry 16(7):738–750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fitz NF et al (2010) Liver X receptor agonist treatment ameliorates amyloid pathology and memory deficits caused by high-fat diet in APP23 mice. J Neurosci 30(20):6862–6872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lee JM et al (2011) A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects. Nature 474(7352):506–510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dong J et al (2016) Nurr1-based therapies for Parkinson’s disease. CNS Neurosci Ther 22(5):351–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Robinson-Rechavi M, Escriva Garcia H, Laudet V (2003) The nuclear receptor superfamily. J Cell Sci 116(Pt 4):585–586

    Article  PubMed  Google Scholar 

  13. Mey J, McCaffery P (2004) Retinoic acid signaling in the nervous system of adult vertebrates. Neuroscientist 10(5):409–421

    Article  CAS  PubMed  Google Scholar 

  14. Skerrett R, Malm T, Landreth G (2014) Nuclear receptors in neurodegenerative diseases. Neurobiol Dis 72 Pt A:104–116

    Article  PubMed  CAS  Google Scholar 

  15. Sandoval-Hernandez AG et al (2015) Role of liver X receptor in AD pathophysiology. PLoS One 10(12):e0145467

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Kumar RA et al (2008) Initial association of NR2E1 with bipolar disorder and identification of candidate mutations in bipolar disorder, schizophrenia, and aggression through resequencing. Am J Med Genet B Neuropsychiatr Genet 147B(6):880–889

    Article  CAS  PubMed  Google Scholar 

  17. Stergiopoulos A, Politis PK (2013) The role of nuclear receptors in controlling the fine balance between proliferation and differentiation of neural stem cells. Arch Biochem Biophys 534(1–2):27–37

    Article  CAS  PubMed  Google Scholar 

  18. Androutsellis-Theotokis A et al (2013) Expression profiles of the nuclear receptors and their transcriptional coregulators during differentiation of neural stem cells. Horm Metab Res 45(2):159–168

    CAS  PubMed  Google Scholar 

  19. Wang T, Xiong JQ (2016) The orphan nuclear receptor TLX/NR2E1 in neural stem cells and diseases. Neurosci Bull 32(1):108–114

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Maden M (2001) Role and distribution of retinoic acid during CNS development. Int Rev Cytol 209:1–77

    Article  CAS  PubMed  Google Scholar 

  21. Bernal J (2007) Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab 3(3):249–259

    Article  CAS  PubMed  Google Scholar 

  22. Lazar MA (1993) Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr Rev 14(2):184–193

    CAS  PubMed  Google Scholar 

  23. Konig S, Moura Neto V (2002) Thyroid hormone actions on neural cells. Cell Mol Neurobiol 22(5–6):517–544

    Article  PubMed  Google Scholar 

  24. St Germain DL, Galton VA, Hernandez A (2009) Minireview: defining the roles of the iodothyronine deiodinases: current concepts and challenges. Endocrinology 150(3):1097–1107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lazar MA, Berrodin TJ, Harding HP (1991) Differential DNA binding by monomeric, homodimeric, and potentially heteromeric forms of the thyroid hormone receptor. Mol Cell Biol 11(10):5005–5015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Forman BM et al (1992) Half-site spacing and orientation determines whether thyroid hormone and retinoic acid receptors and related factors bind to DNA response elements as monomers, homodimers, or heterodimers. Mol Endocrinol 6(3):429–442

    CAS  PubMed  Google Scholar 

  27. Hsu JH et al (1995) Retinoid-X receptor (RXR) differentially augments thyroid hormone response in cell lines as a function of the response element and endogenous RXR content. Endocrinology 136(2):421–430

    Article  CAS  PubMed  Google Scholar 

  28. Falcone M et al (1992) Antipeptide polyclonal antibodies specifically recognize each human thyroid hormone receptor isoform. Endocrinology 131(5):2419–2429

    Article  CAS  PubMed  Google Scholar 

  29. Hodin RA, Lazar MA, Chin WW (1990) Differential and tissue-specific regulation of the multiple rat c-erbA messenger RNA species by thyroid hormone. J Clin Investig 85(1):101–105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yen PM (2001) Physiological and molecular basis of thyroid hormone action. Physiol Rev 81(3):1097–1142

    CAS  PubMed  Google Scholar 

  31. Wallis K et al (2010) The thyroid hormone receptor alpha1 protein is expressed in embryonic postmitotic neurons and persists in most adult neurons. Mol Endocrinol 24(10):1904–1916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Schwartz HL et al (1992) Quantitation of rat tissue thyroid hormone binding receptor isoforms by immunoprecipitation of nuclear triiodothyronine binding capacity. J Biol Chem 267(17):11794–11799

    CAS  PubMed  Google Scholar 

  33. Heuer H, Mason CA (2003) Thyroid hormone induces cerebellar Purkinje cell dendritic development via the thyroid hormone receptor alpha1. J Neurosci 23(33):10604–10612

    CAS  PubMed  Google Scholar 

  34. Lechan RM et al (1993) Immunocytochemical delineation of thyroid hormone receptor beta 2-like immunoreactivity in the rat central nervous system. Endocrinology 132(6):2461–2469

    Article  CAS  PubMed  Google Scholar 

  35. Desouza LA et al (2005) Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain. Mol Cell Neurosci 29(3):414–426

    Article  CAS  PubMed  Google Scholar 

  36. Porterfield SP, Hendrich CE (1993) The role of thyroid hormones in prenatal and neonatal neurological development—current perspectives. Endocr Rev 14(1):94–106

    CAS  PubMed  Google Scholar 

  37. Mohan V et al (2012) Maternal thyroid hormone deficiency affects the fetal neocorticogenesis by reducing the proliferating pool, rate of neurogenesis and indirect neurogenesis. Exp Neurol 237(2):477–488

    Article  CAS  PubMed  Google Scholar 

  38. Pathak A et al (2011) Maternal thyroid hormone before the onset of fetal thyroid function regulates reelin and downstream signaling cascade affecting neocortical neuronal migration. Cereb Cortex 21(1):11–21

    Article  PubMed  Google Scholar 

  39. Cheng SY (2005) Thyroid hormone receptor mutations and disease: beyond thyroid hormone resistance. Trends Endocrinol Metab 16(4):176–182

    Article  CAS  PubMed  Google Scholar 

  40. Chen C et al (2012) Thyroid hormone promotes neuronal differentiation of embryonic neural stem cells by inhibiting STAT3 signaling through TRalpha1. Stem Cells Dev 21(14):2667–2681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chen C et al (2015) Thyroid hormone-Otx2 signaling is required for embryonic ventral midbrain neural stem cells differentiated into dopamine neurons. Stem Cells Dev 24(15):1751–1765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lee LR et al (1994) Thyroid hormone receptor-alpha inhibits retinoic acid-responsive gene expression and modulates retinoic acid-stimulated neural differentiation in mouse embryonic stem cells. Mol Endocrinol 8(6):746–756

    CAS  PubMed  Google Scholar 

  43. Fauquier T et al (2014) Purkinje cells and Bergmann glia are primary targets of the TRalpha1 thyroid hormone receptor during mouse cerebellum postnatal development. Development 141(1):166–175

    Article  CAS  PubMed  Google Scholar 

  44. Johe KK et al (1996) Single factors direct the differentiation of stem cells from the fetal and adult central nervous system. Genes Dev 10(24):3129–3140

    Article  CAS  PubMed  Google Scholar 

  45. Marziali LN, Garcia CI, Pasquini JM (2015) Transferrin and thyroid hormone converge in the control of myelinogenesis. Exp Neurol 265:129–141

    Article  CAS  PubMed  Google Scholar 

  46. Marziali LN et al (2016) Combined effects of transferrin and thyroid hormone during oligodendrogenesis in vitro. Glia 64(11):1879–1891

    Article  CAS  PubMed  Google Scholar 

  47. Baxi EG et al (2014) A selective thyroid hormone beta receptor agonist enhances human and rodent oligodendrocyte differentiation. Glia 62(9):1513–1529

    Article  PubMed  PubMed Central  Google Scholar 

  48. Ambrogini P et al (2005) Thyroid hormones affect neurogenesis in the dentate gyrus of adult rat. Neuroendocrinology 81(4):244–253

    Article  CAS  PubMed  Google Scholar 

  49. Kapoor R et al (2010) Unliganded thyroid hormone receptor alpha1 impairs adult hippocampal neurogenesis. FASEB J 24(12):4793–4805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kapoor R et al (2011) Loss of thyroid hormone receptor beta is associated with increased progenitor proliferation and NeuroD positive cell number in the adult hippocampus. Neurosci Lett 487(2):199–203

    Article  CAS  PubMed  Google Scholar 

  51. Lemkine GF et al (2005) Adult neural stem cell cycling in vivo requires thyroid hormone and its alpha receptor. FASEB J 19(7):863–865

    CAS  PubMed  Google Scholar 

  52. Lopez-Juarez A et al (2012) Thyroid hormone signaling acts as a neurogenic switch by repressing Sox2 in the adult neural stem cell niche. Cell Stem Cell 10(5):531–543

    Article  CAS  PubMed  Google Scholar 

  53. Morte B et al (2004) Aberrant maturation of astrocytes in thyroid hormone receptor alpha 1 knockout mice reveals an interplay between thyroid hormone receptor isoforms. Endocrinology 145(3):1386–1391

    Article  CAS  PubMed  Google Scholar 

  54. Fernandez M et al (2004) Thyroid hormone participates in the regulation of neural stem cells and oligodendrocyte precursor cells in the central nervous system of adult rat. Eur J Neurosci 20(8):2059–2070

    Article  CAS  PubMed  Google Scholar 

  55. MacDonald PN et al (2001) Vitamin D receptor and nuclear receptor coactivators: crucial interactions in vitamin D-mediated transcription. Steroids 66(3–5):171–176

    Article  CAS  PubMed  Google Scholar 

  56. Whitfield GK et al (1995) A highly conserved region in the hormone-binding domain of the human vitamin D receptor contains residues vital for heterodimerization with retinoid X receptor and for transcriptional activation. Mol Endocrinol 9(9):1166–1179

    CAS  PubMed  Google Scholar 

  57. Eyles DW et al (2005) Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 29(1):21–30

    Article  CAS  PubMed  Google Scholar 

  58. Prufer K et al (1999) Distribution of 1,25-dihydroxyvitamin D3 receptor immunoreactivity in the rat brain and spinal cord. J Chem Neuroanat 16(2):135–145

    Article  CAS  PubMed  Google Scholar 

  59. Tague SE, Smith PG (2011) Vitamin D receptor and enzyme expression in dorsal root ganglia of adult female rats: modulation by ovarian hormones. J Chem Neuroanat 41(1):1–12

    Article  CAS  PubMed  Google Scholar 

  60. Eyles DW, Burne TH, McGrath JJ (2013) Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol 34(1):47–64

    Article  CAS  PubMed  Google Scholar 

  61. Kesby JP et al (2011) The effects of vitamin D on brain development and adult brain function. Mol Cell Endocrinol 347(1–2):121–127

    Article  CAS  PubMed  Google Scholar 

  62. Burkert R, McGrath J, Eyles D (2003) Vitamin D receptor expression in the embryonic rat brain. Neurosci Res Commun 33(1):63–71

    Article  CAS  Google Scholar 

  63. Eyles D et al (2003) Vitamin D3 and brain development. Neuroscience 118(3):641–653

    Article  CAS  PubMed  Google Scholar 

  64. Ko P et al (2004) Maternal vitamin D3 deprivation and the regulation of apoptosis and cell cycle during rat brain development. Brain Res Dev Brain Res 153(1):61–68

    Article  CAS  PubMed  Google Scholar 

  65. Cui X et al (2007) Maternal vitamin D depletion alters neurogenesis in the developing rat brain. Int J Dev Neurosci 25(4):227–232

    Article  CAS  PubMed  Google Scholar 

  66. Marini F et al (2010) Effect of 1alpha, 25-dihydroxyvitamin D3 in embryonic hippocampal cells. Hippocampus 20(6):696–705

    CAS  PubMed  Google Scholar 

  67. Cui X et al (2010) Maternal vitamin D deficiency alters the expression of genes involved in dopamine specification in the developing rat mesencephalon. Neurosci Lett 486(3):220–223

    Article  CAS  PubMed  Google Scholar 

  68. Feron F et al (2005) Developmental vitamin D3 deficiency alters the adult rat brain. Brain Res Bull 65(2):141–148

    Article  CAS  PubMed  Google Scholar 

  69. Keilhoff G, Grecksch G, Becker A (2010) Haloperidol normalized prenatal vitamin D depletion-induced reduction of hippocampal cell proliferation in adult rats. Neurosci Lett 476(2):94–98

    Article  CAS  PubMed  Google Scholar 

  70. Zhu Y et al (2012) Abnormal neurogenesis in the dentate gyrus of adult mice lacking 1,25-dihydroxy vitamin D3 (1,25-(OH)2 D3). Hippocampus 22(3):421–433

    Article  CAS  PubMed  Google Scholar 

  71. Shirazi HA et al (2015) 1,25-Dihydroxyvitamin D3 enhances neural stem cell proliferation and oligodendrocyte differentiation. Exp Mol Pathol 98(2):240–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Hall JM, Couse JF, Korach KS (2001) The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem 276(40):36869–36872

    Article  CAS  PubMed  Google Scholar 

  73. Levin ER (2005) Integration of the extranuclear and nuclear actions of estrogen. Mol Endocrinol 19(8):1951–1959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Rollerova E, Urbancikova M (2000) Intracellular estrogen receptors, their characterization and function (Review). Endocr Regul 34(4):203–218

    CAS  PubMed  Google Scholar 

  75. Fan X et al (2010) ERbeta in CNS: new roles in development and function. Prog Brain Res 181:233–250

    Article  CAS  PubMed  Google Scholar 

  76. Luine VN (2014) Estradiol and cognitive function: past, present and future. Horm Behav 66(4):602–618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Hamilton KJ et al (2017) Estrogen hormone biology. Curr Topics Dev Biol 125:109–146

    Article  Google Scholar 

  78. Thomas C, Gustafsson JA (2015) Estrogen receptor mutations and functional consequences for breast cancer. Trends Endocrinol Metab 26(9):467–476

    Article  CAS  PubMed  Google Scholar 

  79. Brannvall K, Korhonen L, Lindholm D (2002) Estrogen-receptor-dependent regulation of neural stem cell proliferation and differentiation. Mol Cell Neurosci 21(3):512–520

    Article  CAS  PubMed  Google Scholar 

  80. Okada M et al (2008) Effects of estrogens on proliferation and differentiation of neural stem/progenitor cells. Biomed Res 29(3):163–170

    Article  CAS  PubMed  Google Scholar 

  81. Okada M et al (2010) Estrogen stimulates proliferation and differentiation of neural stem/progenitor cells through different signal transduction pathways. Int J Mol Sci 11(10):4114–4123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kishi Y et al (2005) Estrogen promotes differentiation and survival of dopaminergic neurons derived from human neural stem cells. J Neurosci Res 79(3):279–286

    Article  CAS  PubMed  Google Scholar 

  83. Wang L et al (2003) Estrogen receptor (ER)beta knockout mice reveal a role for ERbeta in migration of cortical neurons in the developing brain. Proc Natl Acad Sci USA 100(2):703–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Wang L et al (2001) Morphological abnormalities in the brains of estrogen receptor beta knockout mice. Proc Natl Acad Sci USA 98(5):2792–2796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Tanapat P et al (1999) Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci 19(14):5792–5801

    CAS  PubMed  Google Scholar 

  86. Isgor C, Watson SJ (2005) Estrogen receptor alpha and beta mRNA expressions by proliferating and differentiating cells in the adult rat dentate gyrus and subventricular zone. Neuroscience 134(3):847–856

    Article  CAS  PubMed  Google Scholar 

  87. Mazzucco CA et al (2006) Both estrogen receptor alpha and estrogen receptor beta agonists enhance cell proliferation in the dentate gyrus of adult female rats. Neuroscience 141(4):1793–1800

    Article  CAS  PubMed  Google Scholar 

  88. Liu F et al (2008) Activation of estrogen receptor-beta regulates hippocampal synaptic plasticity and improves memory. Nat Neurosci 11(3):334–343

    Article  CAS  PubMed  Google Scholar 

  89. Jover T et al (2002) Estrogen protects against global ischemia-induced neuronal death and prevents activation of apoptotic signaling cascades in the hippocampal CA1. J Neurosci 22(6):2115–2124

    CAS  PubMed  Google Scholar 

  90. Kim K et al (2007) Suppressive effects of bisphenol A on the proliferation of neural progenitor cells. J Toxicol Environ Health A 70(15–16):1288–1295

    Article  CAS  PubMed  Google Scholar 

  91. Sakamoto H et al (2003) Dendritic growth and spine formation in response to estrogen in the developing Purkinje cell. Endocrinology 144(10):4466–4477

    Article  CAS  PubMed  Google Scholar 

  92. Oakley RH, Cidlowski JA (2011) Cellular processing of the glucocorticoid receptor gene and protein: new mechanisms for generating tissue-specific actions of glucocorticoids. J Biol Chem 286(5):3177–3184

    Article  CAS  PubMed  Google Scholar 

  93. Hollenberg SM et al (1985) Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 318(6047):635–641

    Article  CAS  PubMed  Google Scholar 

  94. de Kloet ER, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6(6):463–475

    Article  PubMed  CAS  Google Scholar 

  95. Quax RA et al (2013) Glucocorticoid sensitivity in health and disease. Nat Rev Endocrinol 9(11):670–686

    Article  CAS  PubMed  Google Scholar 

  96. Egeland M, Zunszain PA, Pariante CM (2015) Molecular mechanisms in the regulation of adult neurogenesis during stress. Nat Rev Neurosci 16(4):189–200

    Article  CAS  PubMed  Google Scholar 

  97. Croxtall JD, Choudhury Q, Flower RJ (2000) Glucocorticoids act within minutes to inhibit recruitment of signalling factors to activated EGF receptors through a receptor-dependent, transcription-independent mechanism. Br J Pharmacol 130(2):289–298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Goodwin JE et al (2015) Endothelial glucocorticoid receptor suppresses atherogenesis—brief report. Arterioscler Thromb Vasc Biol 35(4):779–782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Kino T (2000) Glucocorticoid Receptor. In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc. Available via: https://www.ncbi.nlm.nih.gov/books/NBK279171/. Accessed 13 June 2017

  100. Rhen T, Cidlowski JA (2005) Antiinflammatory action of glucocorticoids—new mechanisms for old drugs. N Engl J Med 353(16):1711–1723

    Article  CAS  PubMed  Google Scholar 

  101. Chrousos GP, Charmandari E, Kino T (2004) Glucocorticoid action networks—an introduction to systems biology. J Clin Endocrinol Metab 89(2):563–564

    Article  CAS  PubMed  Google Scholar 

  102. Chrousos GP (2004) The glucocorticoid receptor gene, longevity, and the complex disorders of Western societies. Am J Med 117(3):204–207

    Article  CAS  PubMed  Google Scholar 

  103. Yeh TF et al (2004) Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. N Engl J Med 350(13):1304–1313

    Article  CAS  PubMed  Google Scholar 

  104. Modi N et al (2001) The effects of repeated antenatal glucocorticoid therapy on the developing brain. Pediatr Res 50(5):581–585

    Article  CAS  PubMed  Google Scholar 

  105. Tsiarli MA, Paula A (2013) Monaghan, and D.B. Defranco, Differential subcellular localization of the glucocorticoid receptor in distinct neural stem and progenitor populations of the mouse telencephalon in vivo. Brain Res 1523:10–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Fukumoto K et al (2009) Detrimental effects of glucocorticoids on neuronal migration during brain development. Mol Psychiatry 14(12):1119–1131

    Article  CAS  PubMed  Google Scholar 

  107. Sundberg M et al (2006) Glucocorticoid hormones decrease proliferation of embryonic neural stem cells through ubiquitin-mediated degradation of cyclin D1. J Neurosci 26(20):5402–5410

    Article  CAS  PubMed  Google Scholar 

  108. Bose R et al (2010) Glucocorticoids induce long-lasting effects in neural stem cells resulting in senescence-related alterations. Cell Death Dis 1:e92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Sze CI et al (2013) The role of glucocorticoid receptors in dexamethasone-induced apoptosis of neuroprogenitor cells in the hippocampus of rat pups. Mediat Inflamm 2013:628094

    Article  CAS  Google Scholar 

  110. Samarasinghe RA et al (2011) Nongenomic glucocorticoid receptor action regulates gap junction intercellular communication and neural progenitor cell proliferation. Proc Natl Acad Sci USA 108(40):16657–16662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Noguchi KK et al (2008) Acute neonatal glucocorticoid exposure produces selective and rapid cerebellar neural progenitor cell apoptotic death. Cell Death Differ 15(10):1582–1592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Anacker C et al (2013) Glucocorticoid-related molecular signaling pathways regulating hippocampal neurogenesis. Neuropsychopharmacology 38(5):872–883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Wu J et al (2013) Ginsenoside Rg1 facilitates neural differentiation of mouse embryonic stem cells via GR-dependent signaling pathway. Neurochem Int 62(1):92–102

    Article  CAS  PubMed  Google Scholar 

  114. van Eekelen JA, Bohn MC, de Kloet ER (1991) Postnatal ontogeny of mineralocorticoid and glucocorticoid receptor gene expression in regions of the rat tel- and diencephalon. Brain Res Dev Brain Res 61(1):33–43

    Article  PubMed  Google Scholar 

  115. Fuxe K et al (1985) Mapping of glucocorticoid receptor immunoreactive neurons in the rat tel- and diencephalon using a monoclonal antibody against rat liver glucocorticoid receptor. Endocrinology 117(5):1803–1812

    Article  CAS  PubMed  Google Scholar 

  116. Kino T (2015) Stress, glucocorticoid hormones, and hippocampal neural progenitor cells: implications to mood disorders. Front Physiol 6:230

    Article  PubMed  PubMed Central  Google Scholar 

  117. Murray F, Smith DW, Hutson PH (2008) Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice. Eur J Pharmacol 583(1):115–127

    Article  CAS  PubMed  Google Scholar 

  118. Reimer R et al (2009) Nestin modulates glucocorticoid receptor function by cytoplasmic anchoring. PLoS One 4(6):e6084

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Cameron HA, Gould E (1994) Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience 61(2):203–209

    Article  CAS  PubMed  Google Scholar 

  120. Wong EY, Herbert J (2006) Raised circulating corticosterone inhibits neuronal differentiation of progenitor cells in the adult hippocampus. Neuroscience 137(1):83–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Brummelte S, Galea LA (2010) Chronic high corticosterone reduces neurogenesis in the dentate gyrus of adult male and female rats. Neuroscience 168(3):680–690

    Article  CAS  PubMed  Google Scholar 

  122. Kim JB et al (2004) Dexamethasone inhibits proliferation of adult hippocampal neurogenesis in vivo and in vitro. Brain Res 1027(1–2):1–10

    Article  CAS  PubMed  Google Scholar 

  123. Fitzsimons CP et al (2013) Knockdown of the glucocorticoid receptor alters functional integration of newborn neurons in the adult hippocampus and impairs fear-motivated behavior. Mol Psychiatry 18(9):993–1005

    Article  CAS  PubMed  Google Scholar 

  124. Almeida OF et al (2000) Subtle shifts in the ratio between pro- and antiapoptotic molecules after activation of corticosteroid receptors decide neuronal fate. FASEB J 14(5):779–790

    CAS  PubMed  Google Scholar 

  125. Wagner K et al (2009) Prolactin induces MAPK signaling in neural progenitors without alleviating glucocorticoid-induced inhibition of in vitro neurogenesis. Cell Physiol Biochem 24(5–6):397–406

    Article  CAS  PubMed  Google Scholar 

  126. Schroter A et al (2009) High-dose corticosteroids after spinal cord injury reduce neural progenitor cell proliferation. Neuroscience 161(3):753–763

    Article  CAS  PubMed  Google Scholar 

  127. Matsusue Y et al (2014) Distribution of corticosteroid receptors in mature oligodendrocytes and oligodendrocyte progenitors of the adult mouse brain. J Histochem Cytochem 62(3):211–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Chetty S et al (2014) Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus. Mol Psychiatry 19(12):1275–1283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. de Kloet ER et al (2000) Brain mineralocorticoid receptors and centrally regulated functions. Kidney Int 57(4):1329–1336

    Article  PubMed  Google Scholar 

  130. Farman N, Bocchi B (2000) Mineralocorticoid selectivity: molecular and cellular aspects. Kidney Int 57(4):1364–1369

    Article  CAS  PubMed  Google Scholar 

  131. Pascual-Le Tallec L, Lombes M (2005) The mineralocorticoid receptor: a journey exploring its diversity and specificity of action. Mol Endocrinol 19(9):2211–2221

    Article  CAS  PubMed  Google Scholar 

  132. Martinerie L et al (2013) The mineralocorticoid signaling pathway throughout development: expression, regulation and pathophysiological implications. Biochimie 95(2):148–157

    Article  CAS  PubMed  Google Scholar 

  133. Reul JM, de Kloet ER (1985) Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology 117(6):2505–2511

    Article  CAS  PubMed  Google Scholar 

  134. Marzolla V et al (2012) The role of the mineralocorticoid receptor in adipocyte biology and fat metabolism. Mol Cell Endocrinol 350(2):281–288

    Article  CAS  PubMed  Google Scholar 

  135. ter Heegde F, De Rijk RH, Vinkers CH (2015) The brain mineralocorticoid receptor and stress resilience. Psychoneuroendocrinology 52:92–110

    Article  PubMed  CAS  Google Scholar 

  136. Le Menuet D, Lombes M (2014) The neuronal mineralocorticoid receptor: from cell survival to neurogenesis. Steroids 91:11–19

    Article  PubMed  CAS  Google Scholar 

  137. Berger S et al (2006) Loss of the limbic mineralocorticoid receptor impairs behavioral plasticity. Proc Natl Acad Sci USA 103(1):195–200

    Article  CAS  PubMed  Google Scholar 

  138. Crochemore C et al (2005) Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation. Mol Psychiatry 10(8):790–798

    Article  CAS  PubMed  Google Scholar 

  139. Fischer AK et al (2002) The prototypic mineralocorticoid receptor agonist aldosterone influences neurogenesis in the dentate gyrus of the adrenalectomized rat. Brain Res 947(2):290–293

    Article  CAS  PubMed  Google Scholar 

  140. Gass P et al (2000) Genetic Disruption of Mineralocorticoid Receptor Leads to Impaired Neurogenesis and Granule Cell Degeneration in the Hippocampus of Adult Mice. EMBO Rep 1(5):447–451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. di Masi A et al (2015) Retinoic acid receptors: from molecular mechanisms to cancer therapy. Mol Aspects Med 41:1–115

    Article  PubMed  CAS  Google Scholar 

  142. Maden M (2007) Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci 8(10):755–765

    Article  CAS  PubMed  Google Scholar 

  143. Mizee MR et al (2013) Retinoic acid induces blood–brain barrier development. J Neurosci 33(4):1660–1671

    Article  CAS  PubMed  Google Scholar 

  144. Chiang MY et al (1998) An essential role for retinoid receptors RARbeta and RXRgamma in long-term potentiation and depression. Neuron 21(6):1353–1361

    Article  CAS  PubMed  Google Scholar 

  145. Jokic N et al (2007) Retinoid receptors in chronic degeneration of the spinal cord: observations in a rat model of amyotrophic lateral sclerosis. J Neurochem 103(5):1821–1833

    Article  CAS  PubMed  Google Scholar 

  146. van Neerven S, Kampmann E, Mey J (2008) RAR/RXR and PPAR/RXR signaling in neurological and psychiatric diseases. Prog Neurobiol 85(4):433–451

    Article  PubMed  CAS  Google Scholar 

  147. Goncalves MB et al (2013) Amyloid beta inhibits retinoic acid synthesis exacerbating Alzheimer disease pathology which can be attenuated by an retinoic acid receptor alpha agonist. Eur J Neurosci 37(7):1182–1192

    Article  PubMed  PubMed Central  Google Scholar 

  148. Ribes V et al (2006) Retinaldehyde dehydrogenase 2 (RALDH2)-mediated retinoic acid synthesis regulates early mouse embryonic forebrain development by controlling FGF and sonic hedgehog signaling. Development 133(2):351–361

    Article  CAS  PubMed  Google Scholar 

  149. Jepsen K et al (2007) SMRT-mediated repression of an H3K27 demethylase in progression from neural stem cell to neuron. Nature 450(7168):415–419

    Article  CAS  PubMed  Google Scholar 

  150. Liao WL et al (2008) Modular patterning of structure and function of the striatum by retinoid receptor signaling. Proc Natl Acad Sci USA 105(18):6765–6770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Rataj-Baniowska M et al (2015) Retinoic acid receptor beta controls development of striatonigral projection neurons through FGF-dependent and Meis1-dependent mechanisms. J Neurosci 35(43):14467–14475

    Article  CAS  PubMed  Google Scholar 

  152. Paschaki M et al (2013) Retinoic acid regulates olfactory progenitor cell fate and differentiation. Neural Dev 8:13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Sockanathan S, Jessell TM (1998) Motor neuron-derived retinoid signaling specifies the subtype identity of spinal motor neurons. Cell 94(4):503–514

    Article  CAS  PubMed  Google Scholar 

  154. Sockanathan S, Perlmann T, Jessell TM (2003) Retinoid receptor signaling in postmitotic motor neurons regulates rostrocaudal positional identity and axonal projection pattern. Neuron 40(1):97–111

    Article  CAS  PubMed  Google Scholar 

  155. Goncalves MB et al (2005) Timing of the retinoid-signalling pathway determines the expression of neuronal markers in neural progenitor cells. Dev Biol 278(1):60–70

    Article  CAS  PubMed  Google Scholar 

  156. Bibel M et al (2004) Differentiation of mouse embryonic stem cells into a defined neuronal lineage. Nat Neurosci 7(9):1003–1009

    Article  CAS  PubMed  Google Scholar 

  157. Simandi Z et al (2015) PRMT1 and PRMT8 regulate retinoic acid-dependent neuronal differentiation with implications to neuropathology. Stem Cells 33(3):726–741

    Article  CAS  PubMed  Google Scholar 

  158. Mazzoni EO et al (2013) Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals. Nat Neurosci 16(9):1191–1198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Calder EL et al (2015) Retinoic acid-mediated regulation of GLI3 enables efficient motoneuron derivation from human ESCs in the absence of extrinsic SHH activation. J Neurosci 35(33):11462–11481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Mey J (2006) New therapeutic target for CNS injury? The role of retinoic acid signaling after nerve lesions. J Neurobiol 66(7):757–779

    Article  CAS  PubMed  Google Scholar 

  161. Haskell GT, LaMantia AS (2005) Retinoic acid signaling identifies a distinct precursor population in the developing and adult forebrain. J Neurosci 25(33):7636–7647

    Article  CAS  PubMed  Google Scholar 

  162. Goncalves MB et al (2009) Sequential RARbeta and alpha signalling in vivo can induce adult forebrain neural progenitor cells to differentiate into neurons through Shh and FGF signalling pathways. Dev Biol 326(2):305–313

    Article  CAS  PubMed  Google Scholar 

  163. Takahashi J, Palmer TD, Gage FH (1999) Retinoic acid and neurotrophins collaborate to regulate neurogenesis in adult-derived neural stem cell cultures. J Neurobiol 38(1):65–81

    Article  CAS  PubMed  Google Scholar 

  164. Boku S et al (2015) Neonatal maternal separation alters the capacity of adult neural precursor cells to differentiate into neurons via methylation of retinoic acid receptor gene promoter. Biol Psychiatry 77(4):335–344

    Article  CAS  PubMed  Google Scholar 

  165. Kitaoka K et al (2013) The retinoic acid receptor agonist Am 80 increases hippocampal ADAM10 in aged SAMP8 mice. Neuropharmacology 72:58–65

    Article  CAS  PubMed  Google Scholar 

  166. Gong M et al (2013) Retinoic acid receptor beta mediates all-trans retinoic acid facilitation of mesenchymal stem cells neuronal differentiation. Int J Biochem Cell Biol 45(4):866–875

    Article  CAS  PubMed  Google Scholar 

  167. Mangelsdorf DJ et al (1992) Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev 6(3):329–344

    Article  CAS  PubMed  Google Scholar 

  168. Evans RM, Mangelsdorf DJ (2014) Nuclear receptors, RXR, and the big bang. Cell 157(1):255–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Szanto A et al (2004) Retinoid X receptors: X-ploring their (patho)physiological functions. Cell Death Differ 11(Suppl 2):S126–S143

    Article  CAS  PubMed  Google Scholar 

  170. Dolle P et al (1994) Developmental expression of murine retinoid X receptor (RXR) genes. Mech Dev 45(2):91–104

    Article  CAS  PubMed  Google Scholar 

  171. Saga Y et al (1999) Impaired extrapyramidal function caused by the targeted disruption of retinoid X receptor RXRgamma1 isoform. Genes Cells 4(4):219–228

    Article  CAS  PubMed  Google Scholar 

  172. Huang JK et al (2011) Retinoid X receptor gamma signaling accelerates CNS remyelination. Nat Neurosci 14(1):45–53

    Article  CAS  PubMed  Google Scholar 

  173. Riancho J et al (2015) Neuroprotective effect of bexarotene in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Front Cell Neurosci 9:250

    Article  PubMed  PubMed Central  Google Scholar 

  174. Bachmeier C et al (2013) Stimulation of the retinoid X receptor facilitates beta-amyloid clearance across the blood–brain barrier. J Mol Neurosci 49(2):270–276

    Article  CAS  PubMed  Google Scholar 

  175. McFarland K et al (2013) Low dose bexarotene treatment rescues dopamine neurons and restores behavioral function in models of Parkinson’s disease. ACS Chem Neurosci 4(11):1430–1438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Mounier A et al (2015) Bexarotene-activated retinoid X receptors regulate neuronal differentiation and dendritic complexity. J Neurosci 35(34):11862–11876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Berger J, Moller DE (2002) The mechanisms of action of PPARs. Annu Rev Med 53:409–435

    Article  CAS  PubMed  Google Scholar 

  178. Krey G et al (1997) Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol Endocrinol 11(6):779–791

    Article  CAS  PubMed  Google Scholar 

  179. Kliewer SA et al (1992) Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature 358(6389):771–774

    Article  CAS  PubMed  Google Scholar 

  180. Braissant O, Wahli W (1998) Differential expression of peroxisome proliferator-activated receptor-alpha, -beta, and -gamma during rat embryonic development. Endocrinology 139(6):2748–2754

    Article  CAS  PubMed  Google Scholar 

  181. Wada K et al (2006) Peroxisome proliferator-activated receptor gamma-mediated regulation of neural stem cell proliferation and differentiation. J Biol Chem 281(18):12673–12681

    Article  CAS  PubMed  Google Scholar 

  182. Wang SH et al (2009) PPARgamma-mediated advanced glycation end products regulation of neural stem cells. Mol Cell Endocrinol 307(1–2):176–184

    Article  CAS  PubMed  Google Scholar 

  183. Wang SH et al (2011) PPARgamma-mediated advanced glycation end products regulate neural stem cell proliferation but not neural differentiation through the BDNF-CREB pathway. Toxicol Lett 206(3):339–346

    Article  PubMed  CAS  Google Scholar 

  184. Park KS et al (2004) Neuronal differentiation of embryonic midbrain cells by upregulation of peroxisome proliferator-activated receptor-gamma via the JNK-dependent pathway. Exp Cell Res 297(2):424–433

    Article  CAS  PubMed  Google Scholar 

  185. Esmaeili M et al (2016) Pioglitazone significantly prevented decreased rate of neural differentiation of mouse embryonic stem cells which was reduced by Pex11beta knock-down. Neuroscience 312:35–47

    Article  CAS  PubMed  Google Scholar 

  186. Chiang MC et al (2013) PPARgamma regulates the mitochondrial dysfunction in human neural stem cells with tumor necrosis factor alpha. Neuroscience 229:118–129

    Article  CAS  PubMed  Google Scholar 

  187. Chiang MC et al (2016) Rosiglitazone activation of PPARgamma-dependent pathways is neuroprotective in human neural stem cells against amyloid-beta-induced mitochondrial dysfunction and oxidative stress. Neurobiol Aging 40:181–190

    Article  CAS  PubMed  Google Scholar 

  188. Taheri M et al (2015) A ground state of PPARgamma activity and expression is required for appropriate neural differentiation of hESCs. Pharmacol Rep 67(6):1103–1114

    Article  CAS  PubMed  Google Scholar 

  189. Cristiano L et al (2005) Peroxisome proliferator-activated receptors (PPARs) and related transcription factors in differentiating astrocyte cultures. Neuroscience 131(3):577–587

    Article  CAS  PubMed  Google Scholar 

  190. Saluja I, Granneman JG, Skoff RP (2001) PPAR delta agonists stimulate oligodendrocyte differentiation in tissue culture. Glia 33(3):191–204

    Article  CAS  PubMed  Google Scholar 

  191. Mei YQ et al (2016) A flavonoid compound promotes neuronal differentiation of embryonic stem cells via PPAR-beta modulating mitochondrial energy metabolism. PLoS One 11(6):e0157747

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  192. Fuenzalida K et al (2007) Peroxisome proliferator-activated receptor gamma up-regulates the Bcl-2 anti-apoptotic protein in neurons and induces mitochondrial stabilization and protection against oxidative stress and apoptosis. J Biol Chem 282(51):37006–37015

    Article  CAS  PubMed  Google Scholar 

  193. Moreno S, Farioli-Vecchioli S, Ceru MP (2004) Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS. Neuroscience 123(1):131–145

    Article  CAS  PubMed  Google Scholar 

  194. Cimini A et al (2007) PPARs expression in adult mouse neural stem cells: modulation of PPARs during astroglial differentiaton of NSC. PPAR Res 2007:48242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Morales-Garcia JA et al (2011) Peroxisome proliferator-activated receptor gamma ligands regulate neural stem cell proliferation and differentiation in vitro and in vivo. Glia 59(2):293–307

    Article  PubMed  Google Scholar 

  196. Ji MJ et al (2015) Hippocampal PPARdelta overexpression or activation represses stress-induced depressive behaviors and enhances neurogenesis. Int J Neuropsychopharmacol 19(1):083

    Google Scholar 

  197. Iwashita A et al (2007) Neuroprotective efficacy of the peroxisome proliferator-activated receptor delta-selective agonists in vitro and in vivo. J Pharmacol Exp Ther 320(3):1087–1096

    Article  CAS  PubMed  Google Scholar 

  198. Meng QQ et al (2011) Rosiglitazone enhances the proliferation of neural progenitor cells and inhibits inflammation response after spinal cord injury. Neurosci Lett 503(3):191–195

    Article  CAS  PubMed  Google Scholar 

  199. Kersten S, Desvergne B, Wahli W (2000) Roles of PPARs in health and disease. Nature 405(6785):421–424

    Article  CAS  PubMed  Google Scholar 

  200. Peters JM et al (2000) Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). Mol Cell Biol 20(14):5119–5128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Zandi PP et al (2008) Association study of Wnt signaling pathway genes in bipolar disorder. Arch Gen Psychiatry 65(7):785–793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Chawla A et al (2001) Nuclear receptors and lipid physiology: opening the X-files. Science 294(5548):1866–1870

    Article  CAS  PubMed  Google Scholar 

  203. Bensinger SJ, Tontonoz P (2008) Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 454(7203):470–477

    Article  CAS  PubMed  Google Scholar 

  204. Alberti S, Steffensen KR, Gustafsson JA (2000) Structural characterisation of the mouse nuclear oxysterol receptor genes LXRalpha and LXRbeta. Gene 243(1–2):93–103

    Article  CAS  PubMed  Google Scholar 

  205. Janowski BA et al (1996) An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383(6602):728–731

    Article  CAS  PubMed  Google Scholar 

  206. Janowski BA et al (1999) Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc Natl Acad Sci USA 96(1):266–271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Edwards PA, Kennedy MA, Mak PA (2002) LXRs; oxysterol-activated nuclear receptors that regulate genes controlling lipid homeostasis. Vasc Pharmacol 38(4):249–256

    Article  CAS  Google Scholar 

  208. Fu X et al (2001) 27-Hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells. J Biol Chem 276(42):38378–38387

    Article  CAS  PubMed  Google Scholar 

  209. Zhao C, Dahlman-Wright K (2010) Liver X receptor in cholesterol metabolism. J Endocrinol 204(3):233–240

    Article  CAS  PubMed  Google Scholar 

  210. Schroepfer GJ Jr (2000) Oxysterols: modulators of cholesterol metabolism and other processes. Physiol Rev 80(1):361–554

    CAS  PubMed  Google Scholar 

  211. Venkateswaran A et al (2000) Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. Proc Natl Acad Sci USA 97(22):12097–12102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Zelcer N, Tontonoz P (2006) Liver X receptors as integrators of metabolic and inflammatory signaling. J Clin Investig 116(3):607–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Hannedouche S et al (2011) Oxysterols direct immune cell migration via EBI2. Nature 475(7357):524–527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Valledor AF et al (2004) Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis. Proc Natl Acad Sci USA 101(51):17813–17818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Viennois E et al (2011) Targeting liver X receptors in human health: deadlock or promising trail? Expert Opin Ther Targets 15(2):219–232

    Article  CAS  PubMed  Google Scholar 

  216. Bjorkhem I (2009) Are side-chain oxidized oxysterols regulators also in vivo? J Lipid Res 50(Suppl):S213–S218

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  217. Wang L et al (2002) Liver X receptors in the central nervous system: from lipid homeostasis to neuronal degeneration. Proc Natl Acad Sci USA 99(21):13878–13883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Sacchetti P et al (2009) Liver X receptors and oxysterols promote ventral midbrain neurogenesis in vivo and in human embryonic stem cells. Cell Stem Cell 5(4):409–419

    Article  CAS  PubMed  Google Scholar 

  219. Theofilopoulos S et al (2013) Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis. Nat Chem Biol 9(2):126–133

    Article  CAS  PubMed  Google Scholar 

  220. Andersson S et al (2005) Inactivation of liver X receptor beta leads to adult-onset motor neuron degeneration in male mice. Proc Natl Acad Sci USA 102(10):3857–3862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Zelcer N et al (2007) Attenuation of neuroinflammation and Alzheimer’s disease pathology by liver X receptors. Proc Natl Acad Sci USA 104(25):10601–10606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Yu RT et al (1994) Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx. Nature 370(6488):375–379

    Article  CAS  PubMed  Google Scholar 

  223. Mangelsdorf DJ et al (1995) The nuclear receptor superfamily: the second decade. Cell 83(6):835–839

    Article  CAS  PubMed  Google Scholar 

  224. Monaghan AP et al (1995) The mouse homolog of the orphan nuclear receptor tailless is expressed in the developing forebrain. Development 121(3):839–853

    CAS  PubMed  Google Scholar 

  225. Miyawaki T et al (2004) Tlx, an orphan nuclear receptor, regulates cell numbers and astrocyte development in the developing retina. J Neurosci 24(37):8124–8134

    Article  CAS  PubMed  Google Scholar 

  226. Zhang CL et al (2006) Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1. Genes Dev 20(10):1308–1320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Shi Y et al (2004) Expression and function of orphan nuclear receptor TLX in adult neural stem cells. Nature 427(6969):78–83

    Article  CAS  PubMed  Google Scholar 

  228. Li S et al (2012) Characterization of TLX expression in neural stem cells and progenitor cells in adult brains. PLoS One 7(8):e43324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Monaghan AP et al (1997) Defective limbic system in mice lacking the tailless gene. Nature 390(6659):515–517

    Article  CAS  PubMed  Google Scholar 

  230. Land PW, Monaghan AP (2005) Abnormal development of zinc-containing cortical circuits in the absence of the transcription factor Tailless. Brain Res Dev Brain Res 158(1–2):97–101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Roy K et al (2004) The Tlx gene regulates the timing of neurogenesis in the cortex. J Neurosci 24(38):8333–8345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Li W et al (2008) Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain. Mol Endocrinol 22(1):56–64

    Article  CAS  PubMed  Google Scholar 

  233. Yu RT et al (2000) The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision. Proc Natl Acad Sci USA 97(6):2621–2625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Sehgal R et al (2009) BMP7 and SHH regulate Pax2 in mouse retinal astrocytes by relieving TLX repression. Dev Biol 332(2):429–443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Liu HK et al (2008) The nuclear receptor tailless is required for neurogenesis in the adult subventricular zone. Genes Dev 22(18):2473–2478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Elmi M et al (2010) TLX activates MASH1 for induction of neuronal lineage commitment of adult hippocampal neuroprogenitors. Mol Cell Neurosci 45(2):121–131

    Article  CAS  PubMed  Google Scholar 

  237. Niu W et al (2011) Activation of postnatal neural stem cells requires nuclear receptor TLX. J Neurosci 31(39):13816–13828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Obernier K et al (2011) Expression of Tlx in both stem cells and transit amplifying progenitors regulates stem cell activation and differentiation in the neonatal lateral subependymal zone. Stem Cells 29(9):1415–1426

    CAS  PubMed  Google Scholar 

  239. Zhang CL et al (2008) A role for adult TLX-positive neural stem cells in learning and behaviour. Nature 451(7181):1004–1007

    Article  CAS  PubMed  Google Scholar 

  240. Sun G et al (2007) Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation. Proc Natl Acad Sci USA 104(39):15282–15287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. Qu Q et al (2010) Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal. Nat Cell Biol. 12(1):31–40 (sup pp 1–9)

    Article  CAS  PubMed  Google Scholar 

  242. Chavali PL et al (2011) Nuclear orphan receptor TLX induces Oct-3/4 for the survival and maintenance of adult hippocampal progenitors upon hypoxia. J Biol Chem 286(11):9393–9404

    Article  CAS  PubMed  Google Scholar 

  243. Qin S et al (2014) Orphan nuclear receptor TLX regulates astrogenesis by modulating BMP signaling. Front Neurosci 8:74

    Article  PubMed  PubMed Central  Google Scholar 

  244. Murai K et al (2014) Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning and memory in a transgenic mouse model. Proc Natl Acad Sci USA 111(25):9115–9120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. Shimozaki K et al (2012) SRY-box-containing gene 2 regulation of nuclear receptor tailless (Tlx) transcription in adult neural stem cells. J Biol Chem 287(8):5969–5978

    Article  CAS  PubMed  Google Scholar 

  246. Islam MM et al (2015) Enhancer analysis unveils genetic interactions between TLX and SOX2 in neural stem cells and in vivo reprogramming. Stem Cell Rep 5(5):805–815

    Article  CAS  Google Scholar 

  247. Ryan SM et al (2013) Negative regulation of TLX by IL-1beta correlates with an inhibition of adult hippocampal neural precursor cell proliferation. Brain Behav Immun 33:7–13

    Article  CAS  PubMed  Google Scholar 

  248. Green HF, Nolan YM (2012) Unlocking mechanisms in interleukin-1beta-induced changes in hippocampal neurogenesis—a role for GSK-3beta and TLX. Transl Psychiatry 2:e194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. Zhao C et al (2009) A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination. Nat Struct Mol Biol 16(4):365–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Sun G et al (2011) miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells. Nat Commun 2:529

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  251. Huang Y, Liu X, Wang Y (2015) MicroRNA-378 regulates neural stem cell proliferation and differentiation in vitro by modulating Tailless expression. Biochem Biophys Res Commun 466(2):214–220

    Article  CAS  PubMed  Google Scholar 

  252. Ni N et al (2014) Effects of let-7b and TLX on the proliferation and differentiation of retinal progenitor cells in vitro. Sci Rep 4:6671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Zhao C et al (2013) MicroRNA let-7d regulates the TLX/microRNA-9 cascade to control neural cell fate and neurogenesis. Sci Rep 3:1329

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  254. Juarez P et al (2013) Serotonin(2)A/C receptors mediate the aggressive phenotype of TLX gene knockout mice. Behav Brain Res 256:354–361

    Article  CAS  PubMed  Google Scholar 

  255. Kumar RA et al (2007) Absence of mutations in NR2E1 and SNX3 in five patients with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and related phenotypes. BMC Med Genet 8:48

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  256. Park HJ et al (2010) The neural stem cell fate determinant TLX promotes tumorigenesis and genesis of cells resembling glioma stem cells. Mol Cells 30(5):403–408

    Article  CAS  PubMed  Google Scholar 

  257. Liu HK et al (2010) The nuclear receptor tailless induces long-term neural stem cell expansion and brain tumor initiation. Genes Dev 24(7):683–695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  258. Chavali PL et al (2014) TLX activates MMP-2, promotes self-renewal of tumor spheres in neuroblastoma and correlates with poor patient survival. Cell Death Dis 5:e1502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  259. Taylor MD et al (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8(4):323–335

    Article  CAS  PubMed  Google Scholar 

  260. Sharma MK et al (2007) Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res 67(3):890–900

    Article  CAS  PubMed  Google Scholar 

  261. Sobhan PK, Funa K (2017) TLX—its emerging role for neurogenesis in health and disease. Mol Neurobiol 54(1):272–280

    Article  CAS  PubMed  Google Scholar 

  262. Zou Y et al (2012) The nuclear receptor TLX is required for gliomagenesis within the adult neurogenic niche. Mol Cell Biol 32(23):4811–4820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  263. Johansson E et al (2016) Nuclear receptor TLX inhibits TGF-beta signaling in glioblastoma. Exp Cell Res 343(2):118–125

    Article  CAS  PubMed  Google Scholar 

  264. Sobhan PK et al (2017) ASK1 regulates the survival of neuroblastoma cells by interacting with TLX and stabilizing HIF-1alpha. Cell Signal 30:104–117

    Article  CAS  PubMed  Google Scholar 

  265. Wang LH et al (1989) COUP transcription factor is a member of the steroid receptor superfamily. Nature 340(6229):163–166

    Article  CAS  PubMed  Google Scholar 

  266. Park JI, Tsai SY, Tsai MJ (2003) Molecular mechanism of chicken ovalbumin upstream promoter-transcription factor (COUP-TF) actions. Keio J Med 52(3):174–181

    Article  CAS  PubMed  Google Scholar 

  267. Cooney AJ et al (1993) Multiple mechanisms of chicken ovalbumin upstream promoter transcription factor-dependent repression of transactivation by the vitamin D, thyroid hormone, and retinoic acid receptors. J Biol Chem 268(6):4152–4160

    CAS  PubMed  Google Scholar 

  268. Tran P et al (1992) COUP orphan receptors are negative regulators of retinoic acid response pathways. Mol Cell Biol 12(10):4666–4676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  269. Qiu Y et al (1994) Spatiotemporal expression patterns of chicken ovalbumin upstream promoter-transcription factors in the developing mouse central nervous system: evidence for a role in segmental patterning of the diencephalon. Proc Natl Acad Sci USA 91(10):4451–4455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  270. Zhou C et al (1999) The nuclear orphan receptor COUP-TFI is required for differentiation of subplate neurons and guidance of thalamocortical axons. Neuron 24(4):847–859

    Article  CAS  PubMed  Google Scholar 

  271. Tomassy GS et al (2010) Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI. Proc Natl Acad Sci USA 107(8):3576–3581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  272. Lin FJ et al (2011) Coup d’Etat: an orphan takes control. Endocr Rev 32(3):404–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  273. Pereira FA et al (1999) The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development. Genes Dev 13(8):1037–1049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  274. Naka H et al (2008) Requirement for COUP-TFI and II in the temporal specification of neural stem cells in CNS development. Nat Neurosci 11(9):1014–1023

    Article  CAS  PubMed  Google Scholar 

  275. Faedo A et al (2008) COUP-TFI coordinates cortical patterning, neurogenesis, and laminar fate and modulates MAPK/ERK, AKT, and beta-catenin signaling. Cereb Cortex 18(9):2117–2131

    Article  PubMed  Google Scholar 

  276. Zhou X et al (2015) Transcription factors COUP-TFI and COUP-TFII are required for the production of granule cells in the mouse olfactory bulb. Development 142(9):1593–1605

    Article  CAS  PubMed  Google Scholar 

  277. Kim BJ et al (2009) Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) regulates growth and patterning of the postnatal mouse cerebellum. Dev Biol 326(2):378–391

    Article  CAS  PubMed  Google Scholar 

  278. Yamaguchi H et al (2004) The nuclear orphan receptor COUP-TFI is important for differentiation of oligodendrocytes. Dev Biol 266(2):238–251

    Article  CAS  PubMed  Google Scholar 

  279. Qiu Y et al (1997) Null mutation of mCOUP-TFI results in defects in morphogenesis of the glossopharyngeal ganglion, axonal projection, and arborization. Genes Dev 11(15):1925–1937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  280. Armentano M et al (2006) COUP-TFI is required for the formation of commissural projections in the forebrain by regulating axonal growth. Development 133(21):4151–4162

    Article  CAS  PubMed  Google Scholar 

  281. Inoue M et al (2010) COUP-TFI and -TFII nuclear receptors are expressed in amacrine cells and play roles in regulating the differentiation of retinal progenitor cells. Exp Eye Res 90(1):49–56

    Article  CAS  PubMed  Google Scholar 

  282. Tang K et al (2010) COUP-TFs regulate eye development by controlling factors essential for optic vesicle morphogenesis. Development 137(5):725–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  283. Maxwell MA, Muscat GE (2006) The NR4A subgroup: immediate early response genes with pleiotropic physiological roles. Nucl Recept Signal 4:e002

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  284. Sakurada K et al (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(18):4017–4026

    CAS  PubMed  Google Scholar 

  285. Sacchetti P et al (2001) Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism. J Neurochem 76(5):1565–1572

    Article  CAS  PubMed  Google Scholar 

  286. Ichinose H et al (1999) Molecular cloning of the human Nurr1 gene: characterization of the human gene and cDNAs. Gene 230(2):233–239

    Article  CAS  PubMed  Google Scholar 

  287. Perlmann T, Jansson L (1995) A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1. Genes Dev 9(7):769–782

    Article  CAS  PubMed  Google Scholar 

  288. Zetterstrom RH et al (1996) Retinoid X receptor heterodimerization and developmental expression distinguish the orphan nuclear receptors NGFI-B, Nurr1, and Nor1. Mol Endocrinol 10(12):1656–1666

    CAS  PubMed  Google Scholar 

  289. Le W et al (1999) Selective agenesis of mesencephalic dopaminergic neurons in Nurr1-deficient mice. Exp Neurol 159(2):451–458

    Article  CAS  PubMed  Google Scholar 

  290. Alavian KN et al (2014) The lifelong maintenance of mesencephalic dopaminergic neurons by Nurr1 and engrailed. J Biomed Sci 21:27

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  291. Zetterstrom RH et al (1997) Dopamine neuron agenesis in Nurr1-deficient mice. Science 276(5310):248–250

    Article  CAS  PubMed  Google Scholar 

  292. Shim JW et al (2007) Generation of functional dopamine neurons from neural precursor cells isolated from the subventricular zone and white matter of the adult rat brain using Nurr1 overexpression. Stem Cells 25(5):1252–1262

    Article  CAS  PubMed  Google Scholar 

  293. Lee HS et al (2010) Foxa2 and Nurr1 synergistically yield A9 nigral dopamine neurons exhibiting improved differentiation, function, and cell survival. Stem Cells 28(3):501–512

    CAS  PubMed  Google Scholar 

  294. Flames N, Hobert O (2011) Transcriptional control of the terminal fate of monoaminergic neurons. Annu Rev Neurosci 34:153–184

    Article  CAS  PubMed  Google Scholar 

  295. Smits SM et al (2003) Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic neurons. Eur J Neurosci 18(7):1731–1738

    Article  PubMed  Google Scholar 

  296. Jacobs FM et al (2009) Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression. Development 136(4):531–540

    Article  CAS  PubMed  Google Scholar 

  297. Kim TE et al (2003) Sonic hedgehog and FGF8 collaborate to induce dopaminergic phenotypes in the Nurr1-overexpressing neural stem cell. Biochem Biophys Res Commun 305(4):1040–1048

    Article  CAS  PubMed  Google Scholar 

  298. Kadkhodaei B et al (2009) Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons. J Neurosci 29(50):15923–15932

    Article  CAS  PubMed  Google Scholar 

  299. Heng X et al (2012) Nurr1 regulates Top IIbeta and functions in axon genesis of mesencephalic dopaminergic neurons. Mol Neurodegener 7:4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  300. Kadkhodaei B et al (2013) Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons. Proc Natl Acad Sci USA 110(6):2360–2365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  301. Zhang T et al (2009) NGFI-B nuclear orphan receptor Nurr1 interacts with p53 and suppresses its transcriptional activity. Mol Cancer Res 7(8):1408–1415

    Article  CAS  PubMed  Google Scholar 

  302. Wallen AA et al (2001) Orphan nuclear receptor Nurr1 is essential for Ret expression in midbrain dopamine neurons and in the brain stem. Mol Cell Neurosci 18(6):649–663

    Article  CAS  Google Scholar 

  303. Tomac A et al (1995) Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 373(6512):335–339

    Article  CAS  PubMed  Google Scholar 

  304. Bae EJ et al (2009) Orphan nuclear receptor Nurr1 induces neuron differentiation from embryonic cortical precursor cells via an extrinsic paracrine mechanism. FEBS Lett 583(9):1505–1510

    Article  CAS  PubMed  Google Scholar 

  305. Le WD et al (2003) Mutations in NR4A2 associated with familial Parkinson disease. Nat Genet 33(1):85–89

    Article  CAS  PubMed  Google Scholar 

  306. Wu Y et al (2008) Association of the polymorphisms in NURR1 gene with Parkinson’s disease. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 25(6):693–696

    CAS  PubMed  Google Scholar 

  307. Chu Y et al (2006) Nurr1 in Parkinson’s disease and related disorders. J Comp Neurol 494(3):495–514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  308. Jankovic J, Chen S, Le WD (2005) The role of Nurr1 in the development of dopaminergic neurons and Parkinson’s disease. Prog Neurobiol 77(1–2):128–138

    Article  CAS  PubMed  Google Scholar 

  309. Lee MA et al (2002) Overexpression of midbrain-specific transcription factor Nurr1 modifies susceptibility of mouse neural stem cells to neurotoxins. Neurosci Lett 333(1):74–78

    Article  CAS  PubMed  Google Scholar 

  310. Hoivik EA et al (2010) Molecular aspects of steroidogenic factor 1 (SF-1). Mol Cell Endocrinol 315(1–2):27–39

    Article  CAS  PubMed  Google Scholar 

  311. Lala DS et al (1997) Activation of the orphan nuclear receptor steroidogenic factor 1 by oxysterols. Proc Natl Acad Sci USA 94(10):4895–4900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  312. Krylova IN et al (2005) Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1. Cell 120(3):343–355

    Article  CAS  PubMed  Google Scholar 

  313. Shinoda K et al (1995) Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz-F1 disrupted mice. Dev Dyn 204(1):22–29

    Article  CAS  PubMed  Google Scholar 

  314. Ikeda Y et al (1994) Developmental expression of mouse steroidogenic factor-1, an essential regulator of the steroid hydroxylases. Mol Endocrinol 8(5):654–662

    CAS  PubMed  Google Scholar 

  315. Budefeld T, Tobet SA, Majdic G (2012) Steroidogenic factor 1 and the central nervous system. J Neuroendocrinol 24(1):225–235

    Article  CAS  PubMed  Google Scholar 

  316. Ingraham HA et al (1994) The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis. Genes Dev 8(19):2302–2312

    Article  CAS  PubMed  Google Scholar 

  317. Luo X, Ikeda Y, Parker KL (1994) A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 77(4):481–490

    Article  CAS  PubMed  Google Scholar 

  318. Zhao L et al (2008) Central nervous system-specific knockout of steroidogenic factor 1 results in increased anxiety-like behavior. Mol Endocrinol 22(6):1403–1415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  319. Tran PV et al (2003) Requirement of the orphan nuclear receptor SF-1 in terminal differentiation of ventromedial hypothalamic neurons. Mol Cell Neurosci 22(4):441–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  320. Komada M, Takahashi M, Ikeda Y (2015) Involvement of SF-1 in neurogenesis and neuronal migration in the developing neocortex. Neurosci Lett 600:85–90

    Article  CAS  PubMed  Google Scholar 

  321. Fayard E, Auwerx J, Schoonjans K (2004) LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis. Trends Cell Biol 14(5):250–260

    Article  CAS  PubMed  Google Scholar 

  322. Gofflot F et al (2007) Systematic gene expression mapping clusters nuclear receptors according to their function in the brain. Cell 131(2):405–418

    Article  CAS  PubMed  Google Scholar 

  323. Bookout AL et al (2006) Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 126(4):789–799

    Article  CAS  PubMed  Google Scholar 

  324. Grgurevic N, Tobet S, Majdic G (2005) Widespread expression of liver receptor homolog 1 in mouse brain. Neuro Endocrinol Lett 26(5):541–547

    CAS  PubMed  Google Scholar 

  325. Pare JF et al (2004) The fetoprotein transcription factor (FTF) gene is essential to embryogenesis and cholesterol homeostasis and is regulated by a DR4 element. J Biol Chem 279(20):21206–21216

    Article  CAS  PubMed  Google Scholar 

  326. Gu P et al (2005) Orphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development. Mol Cell Biol 25(9):3492–3505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  327. Wagner RT et al (2010) Canonical Wnt/beta-catenin regulation of liver receptor homolog-1 mediates pluripotency gene expression. Stem Cells 28(10):1794–1804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  328. Heng JC et al (2010) The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell Stem Cell 6(2):167–174

    Article  CAS  PubMed  Google Scholar 

  329. Kaltezioti V et al (2010) Prox1 regulates the notch1-mediated inhibition of neurogenesis. PLoS Biol 8(12):e1000565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  330. Stergiopoulos A, Politis PK (2016) Nuclear receptor NR5A2 controls neural stem cell fate decisions during development. Nat Commun 7:12230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  331. Shi Z et al (2014) Retinoic acid receptor gamma (Rarg) and nuclear receptor subfamily 5, group A, member 2 (Nr5a2) promote conversion of fibroblasts to functional neurons. J Biol Chem 289(10):6415–6428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  332. Greschik H, Schule R (1998) Germ cell nuclear factor: an orphan receptor with unexpected properties. J Mol Med (Berl) 76(12):800–810

    Article  CAS  Google Scholar 

  333. Hummelke GC, Cooney AJ (2001) Germ cell nuclear factor is a transcriptional repressor essential for embryonic development. Front Biosci 6:D1186–D1191

    Article  CAS  PubMed  Google Scholar 

  334. Gu P et al (2005) Orphan nuclear receptor GCNF is required for the repression of pluripotency genes during retinoic acid-induced embryonic stem cell differentiation. Mol Cell Biol 25(19):8507–8519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  335. Yan Z, Jetten AM (2000) Characterization of the repressor function of the nuclear orphan receptor retinoid receptor-related testis-associated receptor/germ cell nuclear factor. J Biol Chem 275(45):35077–35085

    Article  CAS  PubMed  Google Scholar 

  336. Susens U et al (1997) The germ cell nuclear factor mGCNF is expressed in the developing nervous system. Dev Neurosci 19(5):410–420

    Article  CAS  PubMed  Google Scholar 

  337. Chung AC et al (2001) Loss of orphan receptor germ cell nuclear factor function results in ectopic development of the tail bud and a novel posterior truncation. Mol Cell Biol 21(2):663–677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  338. Chen F et al (1994) Cloning of a novel orphan receptor (GCNF) expressed during germ cell development. Mol Endocrinol 8(10):1434–1444

    CAS  PubMed  Google Scholar 

  339. Zhang YL et al (1998) Expression of germ cell nuclear factor (GCNF/RTR) during spermatogenesis. Mol Reprod Dev 50(1):93–102

    Article  CAS  PubMed  Google Scholar 

  340. Lan ZJ et al (2003) Expression of the orphan nuclear receptor, germ cell nuclear factor, in mouse gonads and preimplantation embryos. Biol Reprod 68(1):282–289

    Article  CAS  PubMed  Google Scholar 

  341. Jeong Y, Mangelsdorf DJ (2009) Nuclear receptor regulation of stemness and stem cell differentiation. Exp Mol Med 41(8):525–537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  342. Akamatsu W et al (2009) Suppression of Oct4 by germ cell nuclear factor restricts pluripotency and promotes neural stem cell development in the early neural lineage. J Neurosci 29(7):2113–2124

    Article  CAS  PubMed  Google Scholar 

  343. Mullen EM, Gu P, Cooney AJ (2007) Nuclear receptors in regulation of mouse ES cell pluripotency and differentiation. PPAR Res 2007:61563

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  344. Wang H et al (2016) Germ cell nuclear factor (GCNF) represses Oct4 expression and globally modulates gene expression in human embryonic stem (hES) cells. J Biol Chem 291(16):8644–8652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  345. Gu P et al (2009) Differential recruitment of methylated CpG binding domains by the orphan receptor GCNF initiates the repression and silencing of Oct4 expression. Mol Cell Biol 29(7):1987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  346. Gu P et al (2011) Differential recruitment of methyl CpG-binding domain factors and DNA methyltransferases by the orphan receptor germ cell nuclear factor initiates the repression and silencing of Oct4. Stem Cells 29(7):1041–1051

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  347. Sattler U et al (2004) The expression level of the orphan nuclear receptor GCNF (germ cell nuclear factor) is critical for neuronal differentiation. Mol Endocrinol 18(11):2714–2726

    Article  CAS  PubMed  Google Scholar 

  348. Chung AC et al (2006) Loss of orphan nuclear receptor GCNF function disrupts forebrain development and the establishment of the isthmic organizer. Dev Biol 293(1):13–24

    Article  CAS  PubMed  Google Scholar 

  349. Wang H et al (2014) GCNF-dependent activation of cyclin D1 expression via repression of Mir302a during ESC differentiation. Stem Cells 32(6):1527–1537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to apologize for studies that were not cited due to space limitations. We thank Daphne Antoniou, Elpinickie Ninou, Valeria Kaltezioti, Artemis Michail, and Athanasios Stergiopoulos for helpful discussions and suggestions. The authors work was supported by the Fondation Santé Grant scheme, the Greek State Scholarships Foundation (IKY) and ARISTEIA-II (NeuroNetwk, No. 4786) Grant from General Secretariat of Research and Technology (GSRT), Athens, Greece.

Author information

Author notes

  1. Dimitrios Gkikas and Matina Tsampoula contributed equally to this work.

Authors and Affiliations

  1. Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Efesiou Str, 115 27, Athens, Greece

    Dimitrios Gkikas, Matina Tsampoula & Panagiotis K. Politis

Authors
  1. Dimitrios Gkikas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matina Tsampoula
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Panagiotis K. Politis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Panagiotis K. Politis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gkikas, D., Tsampoula, M. & Politis, P.K. Nuclear receptors in neural stem/progenitor cell homeostasis. Cell. Mol. Life Sci. 74, 4097–4120 (2017). https://doi.org/10.1007/s00018-017-2571-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-017-2571-4

Keywords

Search

Navigation