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Gene Review

otx2-a  -  orthodenticle homeobox 2

Xenopus laevis

Synonyms: Xotx-2, Xotx2, otx-2, otx2, otxA
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High impact information on Otx2

  • Brachyenteron activates the homeobox gene orthopedia in a dose-dependent manner via multiple binding sites with the consensus (A/G)(A/T)(A/T)NTN(A/G)CAC(C/T)T [1].
  • At the molecular level, downregulation of Ras-dva inhibits the expression of several regulators of the anterior neural plate and folds patterning, such as Otx2, BF-1 (also known as Foxg1), Xag2, Pax6, Slug and Sox9, and interferes with FGF8 signaling within the anterior ectoderm [2].
  • On its own, Six3 is unable to induce neural tissue in animal caps, but it can do so in combination with Otx2 [3].
  • Other effects of the ectopic Xanf-1 include cyclopic phenotype and inhibition of the cement gland, both by Otx-2-dependent and -independent mechanisms [4].
  • Activation of Otx-2, Pax-6 and Sox-3 in competent ectoderm occurs in response to the early inducing tissue, the anterior neural plate [5].

Biological context of Otx2


Anatomical context of Otx2

  • While both of these factors prevent the activation of genes specific to the nascent central nervous system, Msx1 inhibits anterior markers, including Otx2 and cement gland-specific genes [11].
  • The border between the transcription domains of Otx2 and Gbx2 is the earliest known marker of the region where the midbrain/hindbrain boundary (MHB) organizer will develop [12].
  • In addition, taking advantage of hormone-inducible versions of Xgbx2a and its antimorph, we show that the ability of Xgbx2a to induce head malformations is restricted to gastrula stages and correlates with its ability to repress Otx2 during the same developmental stages [12].
  • In contrast, the overexpression of a dominant negative form of Nbx during neurula stages suppressed the expression of the neural crest marker Slug and expanded neural markers such as Otx2 and Sox2 [13].
  • The homeobox gene goosecoid has been implicated to play a central role in the Spemann organizer tissue of the vertebrate embryo [9].

Associations of Otx2 with chemical compounds


Regulatory relationships of Otx2

  • Otx2 represses the expression of Xbra and Xwnt-11, and the effects of IGF on gastrulation movements can be partially rescued by antisense Otx2 morpholino oligonucleotide [6].

Other interactions of Otx2

  • Anterior-posterior patterning of the embryo requires the activity of multiple homeobox genes among them Hox, caudal (Cdx, Xcad) and Otx2 [12].
  • Consistent with this, we show that inhibition of IGF signaling or Otx2 function induces Xbra and Xwnt11 expression and convergent extension in ectodermal cells [6].
  • The circadian gene Clock is restricted to the anterior neural plate early in development and is regulated by the neural inducer noggin and the transcription factor Otx2 [15].
  • Homeobox genes like Otx-2 and members of the Hox family have been implicated in this process [16].
  • This later Eomes expression marks a very localized region of the forebrain distinct from that of Otx-2, anterior to that of En-1 and overlapping that of Sox-3 [17].


  1. Brachyury proteins regulate target genes through modular binding sites in a cooperative fashion. Kusch, T., Storck, T., Walldorf, U., Reuter, R. Genes Dev. (2002) [Pubmed]
  2. Ras-dva, a member of novel family of small GTPases, is required for the anterior ectoderm patterning in the Xenopus laevis embryo. Tereshina, M.B., Zaraisky, A.G., Novoselov, V.V. Development (2006) [Pubmed]
  3. Six3 functions in anterior neural plate specification by promoting cell proliferation and inhibiting Bmp4 expression. Gestri, G., Carl, M., Appolloni, I., Wilson, S.W., Barsacchi, G., Andreazzoli, M. Development (2005) [Pubmed]
  4. The homeobox gene, Xanf-1, can control both neural differentiation and patterning in the presumptive anterior neurectoderm of the Xenopus laevis embryo. Ermakova, G.V., Alexandrova, E.M., Kazanskaya, O.V., Vasiliev, O.L., Smith, M.W., Zaraisky, A.G. Development (1999) [Pubmed]
  5. Gene activation during early stages of lens induction in Xenopus. Zygar, C.A., Cook, T.L., Grainger, R.M. Development (1998) [Pubmed]
  6. Antagonistic interaction between IGF and Wnt/JNK signaling in convergent extension in Xenopus embryo. Carron, C., Bourdelas, A., Li, H.Y., Boucaut, J.C., Shi, D.L. Mech. Dev. (2005) [Pubmed]
  7. Structure and expression of an Otx5-related gene in the dogfish Scyliorhinus canicula: evidence for a conserved role of Otx5 and Crxgenes in the specification of photoreceptors. Sauka-Spengler, T., Baratte, B., Shi, L., Mazan, S. Dev. Genes Evol. (2001) [Pubmed]
  8. Cooperative interaction of Xvent-2 and GATA-2 in the activation of the ventral homeobox gene Xvent-1B. Friedle, H., Knöchel, W. J. Biol. Chem. (2002) [Pubmed]
  9. Negative autoregulation of the organizer-specific homeobox gene goosecoid. Danilov, V., Blum, M., Schweickert, A., Campione, M., Steinbeisser, H. J. Biol. Chem. (1998) [Pubmed]
  10. DNA sequences mediating the transcriptional response of the Mix.2 homeobox gene to mesoderm induction. Vize, P.D. Dev. Biol. (1996) [Pubmed]
  11. Inhibitory patterning of the anterior neural plate in Xenopus by homeodomain factors Dlx3 and Msx1. Feledy, J.A., Beanan, M.J., Sandoval, J.J., Goodrich, J.S., Lim, J.H., Matsuo-Takasaki, M., Sato, S.M., Sargent, T.D. Dev. Biol. (1999) [Pubmed]
  12. Gbx2 interacts with Otx2 and patterns the anterior-posterior axis during gastrulation in Xenopus. Tour, E., Pillemer, G., Gruenbaum, Y., Fainsod, A. Mech. Dev. (2002) [Pubmed]
  13. Xenopus Nbx, a novel NK-1 related gene essential for neural crest formation. Kurata, T., Ueno, N. Dev. Biol. (2003) [Pubmed]
  14. The neurotransmitter noradrenaline drives noggin-expressing ectoderm cells to activate N-tubulin and become neurons. Messenger, N.J., Rowe, S.J., Warner, A.E. Dev. Biol. (1999) [Pubmed]
  15. The circadian gene Clock is restricted to the anterior neural plate early in development and is regulated by the neural inducer noggin and the transcription factor Otx2. Green, C.B., Durston, A.J., Morgan, R. Mech. Dev. (2001) [Pubmed]
  16. Patterning of the embryo along the anterior-posterior axis: the role of the caudal genes. Epstein, M., Pillemer, G., Yelin, R., Yisraeli, J.K., Fainsod, A. Development (1997) [Pubmed]
  17. Xenopus eomesodermin is expressed in neural differentiation. Ryan, K., Butler, K., Bellefroid, E., Gurdon, J.B. Mech. Dev. (1998) [Pubmed]
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