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Homo sapiens
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens
Mus musculus
Transcription Factor Encyclopedia  BETA
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Nr2e1 is expressed predominantly in the forebrain and dorsal midbrain regions throughout development[1] and remains expressed in the adult subventricular and subgranular zones, areas of active neurogenesis[2][3][4]. Expression begins as early as E8 in the brain and peaks at E12.5[1], after which expression drops until after birth[5]. At E12.5, expression is high in the lateral telencephalon (dorsal and lateral pallium, and lateral ganglionic eminence), and low in the dorsomedial pallium and medial ganglionic eminence[6]. In the eye, Nr2e1 is expressed in the neural retina and optic stalk at E13[7]. Specifically, Nr2e1 is expressed in retinal progenitor cells, Müller glia, and astrocytes[8], including proangiogenic retinal astrocytes[9]. At E14.5, expression is similar to E12.5 but also in the ventricular zone of the third ventricle[6]. Expression is also observed in the adult retina and is required for vision[10][11][7][12][13]. Nr2e1 is expressed in neural stem cells and co-stains with nestin, RC2, and almost always with BrdU and Ki67[14][15][16][17][18]. Nestin co-expression in the SVZ and SGZ was verified with a β-galactosidase reporter knocked-in at the Nr2e1 locus[14]. Sparse expression was also observed in the cortex[14]. When isolated using FACS, β-gal-positive presumptive NSCs isolated from brain tissue proliferate in NSC-proliferation medium[14].

In vivo, expression is limited to type B neural stem cells (co-stained with Gfap), and not in type C transitly-amplifying progenitors or type A immature migratory neuroblasts[2]. Nr2e1 is also required for the transition from radial glial to astrocyte-like NSCs around P9[16]. Interestingly, a sub-population of excitatory glutamatergic neurons express Nr2e1 as well, where its function is unknown[3].

An Nr2e1 BAC driving cre recombinase crossed to a ROSA26 mouse indicated that expression is found in the subventricular zone, rostral migratory stream, and dentate gyrus of the hippocampus[2]. This expression is confirmed by Allen Brain Atlas in situ hybridization.

In Drosophila, tailless (Nr2e1) does not seem to be self-regulatory[19], consistent with studies of β-gal expression in Nr2e1lacZ/- mice[14].

In Xenopus, Xtll (Nr2e1) expression has been detected in the brain, eye, and testes[10]; however, in mouse, Nr2e1 was not detected in testes[20]. In Fugu, expression is strongly observed in the brain and eye[11].

In vitro, Nr2e1 is detected under proliferation and not differentiation conditions of neural stem cells, wherein it is localized to the nucleus[15]. The regulation of NSC proliferation is primarily in a cell-autonomous fashion, as growth factors from surrounding wild-type cells cannot rescue the proliferation defects of null cells[3].

In the eye, Nr2e1 expression is rapidly downregulated upon contact with blood vessels and levels are regulated by oxygen concentration[9]. Co-expression of VEGF and fibronectin is found in retinal astrocytes, where Nr2e1 is important for establishing the retinal astrocyte extracellular fibronectin network[9].

  1. Monaghan AP et al. The mouse homolog of the orphan nuclear receptor tailless is expressed in the developing forebrain. Development, 121(3):839-53. (PMID 7720587)
  2. Liu HK et al. The nuclear receptor tailless is required for neurogenesis in the adult subventricular zone. Genes Dev., 22(18):2473-8. (PMID 18794344)
  3. Zhang CL et al. A role for adult TLX-positive neural stem cells in learning and behaviour. Nature, 451(7181):1004-7. (PMID 18235445)
  4. Shi Y. Orphan nuclear receptors in drug discovery. Drug Discov. Today, 12(11-12):440-5. (PMID 17532527)
  5. Yu RT et al. Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx. Nature, 370(6488):375-9. (PMID 8047143)
  6. Stenman J et al. Tlx and Pax6 co-operate genetically to establish the pallio-subpallial boundary in the embryonic mouse telencephalon. Development, 130(6):1113-22. (PMID 12571103)
  7. Yu RT et al. The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision. Proc. Natl. Acad. Sci. U.S.A., 97(6):2621-5. (PMID 10706625)
  8. Miyawaki T et al. Tlx, an orphan nuclear receptor, regulates cell numbers and astrocyte development in the developing retina. J. Neurosci., 24(37):8124-34. (PMID 15371513)
  9. Uemura A et al. Tlx acts as a proangiogenic switch by regulating extracellular assembly of fibronectin matrices in retinal astrocytes. J. Clin. Invest., 116(2):369-77. (PMID 16424942)
  10. Hollemann T et al. The Xenopus homologue of the Drosophila gene tailless has a function in early eye development. Development, 125(13):2425-32. (PMID 9609825)
  1. Abrahams BS et al. Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci. Genomics, 80(1):45-53. (PMID 12079282)
  2. Kobayashi M et al. Identification of a photoreceptor cell-specific nuclear receptor. Proc. Natl. Acad. Sci. U.S.A., 96(9):4814-9. (PMID 10220376)
  3. Daniel A et al. The control of cell fate in the embryonic visual system by atonal, tailless and EGFR signaling. Development, 126(13):2945-54. (PMID 10357938)
  4. Shi Y et al. Expression and function of orphan nuclear receptor TLX in adult neural stem cells. Nature, 427(6969):78-83. (PMID 14702088)
  5. Sun G et al. Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation. Proc. Natl. Acad. Sci. U.S.A., 104(39):15282-7. (PMID 17873065)
  6. Li W et al. Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain. Mol. Endocrinol., 22(1):56-64. (PMID 17901127)
  7. Zhao C et al. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination. Nat. Struct. Mol. Biol., 16(4):365-71. (PMID 19330006)
  8. Denli AM et al. miR-9 and TLX: chasing tails in neural stem cells. Nat. Struct. Mol. Biol., 16(4):346-7. (PMID 19343066)
  9. Rudolph KM et al. Complex regulatory region mediating tailless expression in early embryonic patterning and brain development. Development, 124(21):4297-308. (PMID 9334278)
  10. Young KA et al. Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background-dependent. Behav. Brain Res., 132(2):145-58. (PMID 11997145)
Expression (automatically populated)
GNF Expression Atlas 2 Data from U133A and GNF1H Chips
Using GNF ID 207443_at that is linked to Ensembl Transcript ID ENST00000368986
1. Fetal brain
2. Whole brain
3. Temporal lobe
4. Parietal lobe
5. Occipital lobe
6. Prefrontal cortex
7. Cingulate cortex
8. Cerebellum
9. Cerebellum peduncles
10. Amygdala
11. Hypothalamus
12. Thalamus
13. Subthalamic nucleus
14. Caudate nucleus
15. Globus pallidus
16. Olfactory bulb
17. Pons
18. Medulla oblongata
19. Spinal cord
20. Ciliary ganglion
21. Trigeminal ganglion
22. Superior cervical ganglion
23. Dorsal root ganglion
24. Thymus
25. Tonsil
26. Lymph node
27. Bone marrow
28. BM-CD71+ early erythroid
29. BM-CD33+ myeloid
30. BM-CD105+ endothelial
31. BM-CD34+
32. Whole blood
33. PB-BDCA4+ dentritic cells
34. PB-CD14+ monocytes
35. PB-CD56+ NKCells
36. PB-CD4+ Tcells
37. PB-CD8+ Tcells
38. PB-CD19+ Bcells
39. Leukemia lymphoblastic (molt4)
40. 721 B lymphoblasts
41. Lymphoma Burkitts Raji
42. Leukemia promyelocytic (hl60)
43. Lymphoma Burkitts Daudi
44. Leukemia chronic myelogenous (k562)
45. Colorectal adenocarcinoma
46. Appendix
47. Skin
48. Adipocyte
49. Fetal thyroid
50. Thyroid
51. Pituitary gland
52. Adrenal gland
53. Adrenal cortex
54. Prostate
55. Salivary gland
56. Pancreas
57. Pancreatic islets
58. Atrioventricular node
59. Heart
60. Cardiac myocytes
61. Skeletal muscle
62. Tongue
63. Smooth muscle
64. Uterus
65. Uterus corpus
66. Trachea
67. Bronchial epithelial cells
68. Fetal lung
69. Lung
70. Kidney
71. Fetal liver
72. Liver
73. Placenta
74. Testis
75. Testis Leydig cell
76. Testis germ cell
77. Testis interstitial
78. Testis seminiferous tubule
79. Ovary
Mouse Brain Expression Data from Allen Brain Atlas