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Gene Review

otx2  -  orthodenticle homeobox 2

Danio rerio

Synonyms: Homeobox protein OTX2, Orthodenticle homolog 2, SO:0000704, id:ibd2915, zOTX2, ...
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High impact information on otx2

  • Wnt8 is required for the initial subdivision of the neuroectoderm, including onset of posterior gbx1 expression and establishment of the posterior border of otx2 expression [1].
  • A new interface between otx2 and epha4a suggests that the rostralization stops at the caudal part of rhombomere 1 [2].
  • Using these two genes, as well as otx2 and meis3 as anterior and posterior markers, we show that Fgf and Wnt signals suppress expression of anterior genes, including cyp26 [3].
  • The zbmp-2-expressing domain and the neuroectoderm, marked by otx-2 expression, were complementary, suggesting that BMP has a short-range effect in vivo [4].
  • Moreover, mosaic experiments using a constitutively active form of a zebrafish BMP type I receptor (CA-BRIA) demonstrated that the cell-fate conversion, revealed by ectopic expression of gata-3 and repression of otx-2, occurred in a cell-autonomous manner, denying the involvement of the relay mechanism [4].

Biological context of otx2


Anatomical context of otx2

  • Zebrafish early gastrula ectodermal explants are specified to express the neural markers opl (zic1) and otx2, and this expression is prevented by BMP4 [6].

Regulatory relationships of otx2

  • Meanwhile, misexpression of otx2 suppressed the expression of gbx2 in the embryonic brain [7].

Other interactions of otx2

  • By contrast, regional definition of the future MHB in the neuroectoderm by complementary expression of otx2 and gbx1, before the establishment of the complex regulatory cascade at the MHB, is normal in spg embryos [8].
  • It effectively suppressed the anterior neural marker, otx2, but not the posterior marker, hoxb1b [9].
  • This result is consistent with the observation that there is no gap between the expression domains of zbmp-2 and otx-2 [4].
  • Expression analyses show that otx2 and mitfb are not expressed in the prospective RPE of chk, indicating that the retinal homeobox gene rx3 acts upstream of the molecular network controlling RPE specification [10].
  • The system was tested with induced expression of Xactivin(beta)B and X(wnt), which both were shown to induce morphological abnormalities, as well as alterations in the expression patterns of goosecoid and otx2, respectively [11].

Analytical, diagnostic and therapeutic context of otx2

  • Strikingly, our analysis by in situ hybridization demonstrates that the transcription factor, otx2, is up regulated in the olfactory sensory epithelia in response to PEA [5].


  1. Positioning of the midbrain-hindbrain boundary organizer through global posteriorization of the neuroectoderm mediated by Wnt8 signaling. Rhinn, M., Lun, K., Luz, M., Werner, M., Brand, M. Development (2005) [Pubmed]
  2. Isthmus-to-midbrain transformation in the absence of midbrain-hindbrain organizer activity. Jászai, J., Reifers, F., Picker, A., Langenberg, T., Brand, M. Development (2003) [Pubmed]
  3. Distinct roles for Fgf, Wnt and retinoic acid in posteriorizing the neural ectoderm. Kudoh, T., Wilson, S.W., Dawid, I.B. Development (2002) [Pubmed]
  4. In vivo analysis using variants of zebrafish BMPR-IA: range of action and involvement of BMP in ectoderm patterning. Nikaido, M., Tada, M., Takeda, H., Kuroiwa, A., Ueno, N. Development (1999) [Pubmed]
  5. Olfactory imprinting is correlated with changes in gene expression in the olfactory epithelia of the zebrafish. Harden, M.V., Newton, L.A., Lloyd, R.C., Whitlock, K.E. J. Neurobiol. (2006) [Pubmed]
  6. Specification of the enveloping layer and lack of autoneuralization in zebrafish embryonic explants. Sagerström, C.G., Gammill, L.S., Veale, R., Sive, H. Dev. Dyn. (2005) [Pubmed]
  7. gbx2 Homeobox gene is required for the maintenance of the isthmic region in the zebrafish embryonic brain. Kikuta, H., Kanai, M., Ito, Y., Yamasu, K. Dev. Dyn. (2003) [Pubmed]
  8. Spiel-ohne-grenzen/pou2 mediates regional competence to respond to Fgf8 during zebrafish early neural development. Reim, G., Brand, M. Development (2002) [Pubmed]
  9. Inhibition of BMP activity by the FGF signal promotes posterior neural development in zebrafish. Koshida, S., Shinya, M., Nikaido, M., Ueno, N., Schulte-Merker, S., Kuroiwa, A., Takeda, H. Dev. Biol. (2002) [Pubmed]
  10. chokh/rx3 specifies the retinal pigment epithelium fate independently of eye morphogenesis. Rojas-Muñoz, A., Dahm, R., Nüsslein-Volhard, C. Dev. Biol. (2005) [Pubmed]
  11. Hormone-inducible expression of secreted factors in zebrafish embryos. de Graaf, M., Zivkovic, D., Joore, J. Dev. Growth Differ. (1998) [Pubmed]
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