Receptor nomenclature NR2E1
Receptor code 4.10.1:OR:2:E1
Other names MTLL
Molecular information Hs: 385aa, Q9Y466, chr. 6q211
Mm: 385aa, Q64104, chr. 10 B22
DNA binding
   Structure Monomer, homodimer
   HRE core sequence AAGTCA n AAGTCA (DR-1, half-site)
Biologically important isoforms
Tissue distribution Developmental: head ectoderm (developing telencephalon and dorsal midbrain), eye, nose, and proangiogenic astrocytes {Mm} [Northern blot, in situ hybridization, immunohistology]24
Functional assays
Main target genes Activated: RARβ {Hs, Mm, Rn}5; repressed: PAX2 {Hs, Mm, Rn},3 Gfap {Mm}4
Mutant phenotype TLX knockout mice exhibit a marked forebrain phenotype with a reduction in the size of rhinencephalic and limbic structures; in addition, both males and females are more aggressive than usual, and the females lack normal maternal instincts; the knockout mice also exhibit a progressive retinal and optic nerve degeneration with associated blindness {Mm} [knockout]612; a spontaneous mouse mutation exists for the NR2E1 gene called fierce (frc)—this mutation is genetically and phenotypically similar to NR2E1-targeted mutations {Mm} [spontaneous mutation]13
Human disease
  • aa, amino acids; chr., chromosome; HRE, hormone response element; RAR, retinoic acid receptor

  • 1. Finley KD, Taylor BJ, Milstein M, and McKeown M (1997) dissatisfaction, a gene involved in sex-specific behavior and neural development of Drosophila melanogaster. Proc Natl Acad Sci USA 94: 913-918

  • 2. Yu RT, McKeown M, Evans RM, and Umesono K (1994) Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx. Nature (Lond) 370: 375-379

  • 3. Yu RT, Chiang MT, Tanabe T, Kobayashi M, Yasuda K, Evans RM, and Umesono K (2000) The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision. Proc Natl Acad Sci USA 97: 2621-2625

  • 4. Uemura A, Kusuhara S, Wiegand SJ, Yu RT, and Nishikawa S (2006) Tlx acts as a proangiogenic switch by regulating extracellular assembly of fibronectin matrices in retinal astrocytes. J Clin Investig 116: 369-377

  • 5. Kobayashi M, Yu RT, Yasuda K, and Umesono K (2000) Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX. Mol Cell Biol 20: 8731-8739

  • 6. Monaghan AP, Bock D, Gass R, Schwager A, Wolfer DP, Lipp HP, and Schutz G (1997) Defective limbic system in mice lacking the tailless gene. Nature (Lond) 390: 515-517

  • 7. Land PW and Monaghan AP (2003) Expression of the transcription factor, tailless, is required for formation of superficial cortical layers. Cereb Cortex 13: 921-931

  • 8. Land PW and Monaghan AP (2005) Abnormal development of zinc-containing cortical circuits in the absence of the transcription factor Tailless. Brain Res Dev Brain Res 158: 97-101

  • 9. Miyawaki T, Uemura A, Dezawa M, Yu RT, Ide C, Nishikawa S, Honda Y, Tanabe Y, and Tanabe T (2004) Tlx, an orphan nuclear receptor, regulates cell numbers and astrocyte development in the developing retina. J Neurosci 24: 8124-8134

  • 10. Roy K, Kuznicki K, Wu Q, Sun Z, Bock D, Schutz G, Vranich N, and Monaghan AP (2004) The Tlx gene regulates the timing of neurogenesis in the cortex. J Neurosci 24: 8333-8345

  • 11. Roy K, Thiels E, and Monaghan AP (2002) Loss of the tailless gene affects forebrain development and emotional behavior. Physiol Behav 77: 595-600

  • 12. Stenman J, Yu RT, Evans RM, and Campbell K (2003) Tlx and Pax6 co-operate genetically to establish the pallio-subpallial boundary in the embryonic mouse telencephalon. Development 130: 1113-1122

  • 13. Young KA, Berry ML, Mahaffey CL, Saionz JR, Hawes NL, Chang B, Zheng QY, Smith RS, Bronson RT, Nelson RJ, et al. (2002) Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background-dependent. Behav Brain Res 132: 145-158