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 SOX9
Homo sapiens
 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
Mus musculus
 PPARA
Homo sapiens
 Ppara
Mus musculus
 Thrb
Mus musculus
 SNAI2
Homo sapiens
 Tbr1
Mus musculus
Transcription Factor Encyclopedia  BETA
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Overview

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].

References
  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
83 
2. Whole brain
76 
 
3. Temporal lobe
10 
4. Parietal lobe
16 
5. Occipital lobe
32 
6. Prefrontal cortex
100 
7. Cingulate cortex
36 
8. Cerebellum
-7 
9. Cerebellum peduncles
1 
10. Amygdala
99 
11. Hypothalamus
31 
12. Thalamus
-5 
13. Subthalamic nucleus
-21 
14. Caudate nucleus
87 
15. Globus pallidus
33 
16. Olfactory bulb
-4 
17. Pons
12 
18. Medulla oblongata
13 
 
19. Spinal cord
-20 
20. Ciliary ganglion
-56 
21. Trigeminal ganglion
-5 
22. Superior cervical ganglion
-14 
23. Dorsal root ganglion
10 
 
24. Thymus
-42 
25. Tonsil
-16 
26. Lymph node
-24 
27. Bone marrow
-2 
28. BM-CD71+ early erythroid
-17 
29. BM-CD33+ myeloid
1 
30. BM-CD105+ endothelial
12 
31. BM-CD34+
22 
32. Whole blood
-3 
 
33. PB-BDCA4+ dentritic cells
-48 
34. PB-CD14+ monocytes
-37 
35. PB-CD56+ NKCells
13 
36. PB-CD4+ Tcells
-6 
37. PB-CD8+ Tcells
-16 
38. PB-CD19+ Bcells
19 
 
39. Leukemia lymphoblastic (molt4)
-11 
40. 721 B lymphoblasts
-27 
41. Lymphoma Burkitts Raji
12 
42. Leukemia promyelocytic (hl60)
-1 
43. Lymphoma Burkitts Daudi
15 
44. Leukemia chronic myelogenous (k562)
6 
45. Colorectal adenocarcinoma
-14 
 
46. Appendix
17 
47. Skin
3 
48. Adipocyte
5 
49. Fetal thyroid
18 
50. Thyroid
-5 
51. Pituitary gland
-9 
 
52. Adrenal gland
-40 
53. Adrenal cortex
11 
54. Prostate
6 
55. Salivary gland
-25 
56. Pancreas
-14 
57. Pancreatic islets
-6 
 
58. Atrioventricular node
-2 
59. Heart
22 
60. Cardiac myocytes
-20 
61. Skeletal muscle
11 
62. Tongue
-14 
63. Smooth muscle
-19 
64. Uterus
-16 
65. Uterus corpus
14 
66. Trachea
-15 
 
67. Bronchial epithelial cells
19 
68. Fetal lung
-8 
69. Lung
15 
 
70. Kidney
-8 
71. Fetal liver
8 
72. Liver
19 
73. Placenta
-10 
 
74. Testis
-22 
75. Testis Leydig cell
-11 
76. Testis germ cell
-71 
77. Testis interstitial
-21 
78. Testis seminiferous tubule
-31 
79. Ovary
-9 
Mouse Brain Expression Data from Allen Brain Atlas