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Gene Review

OTX2  -  orthodenticle homeobox 2

Gallus gallus

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High impact information on OTX2

  • Implication of OTX2 in pigment epithelium determination and neural retina differentiation [1].
  • Bromodeoxyuridine labeling in combination with immunohistochemistry with anti-OTX2 antiserum and different cell-specific markers were used to determine that OTX2-positive cells are postmitotic neuroblasts undergoing differentiation into several, if not all, of the distinct cell types present in the chick retina [1].
  • Early on, Otx2 expression was diffuse throughout the optic vesicles but became restricted to their dorsal part when the vesicles contacted the surface ectoderm [1].
  • Specification of the meso-isthmo-cerebellar region: the Otx2/Gbx2 boundary [2].
  • Different combinations of signals are responsible for different aspects of this early transient induction: FGF initiates expression of Sox3 and ERNI, retinoic acid can induce Cyp26A1 and only a combination of low levels of FGF8 together with Wnt- and BMP-antagonists can induce Otx2 [3].

Biological context of OTX2

  • A distinct preisthmic histogenetic domain is defined by overlap of Otx2 and Pax2 gene expression in the avian caudal midbrain [4].
  • This was accompanied by down-regulation of Otx2 and BMP7, which implicates that these factors are essential for choroid plexus specification and differentiation [5].
  • During development, a burst of Otx2 mRNA closely matched the timing of HIOMT gene activation in these two tissues [6].

Anatomical context of OTX2

  • The parvicellular isthmic nucleus, although placed inside the midbrain lobe, never expressed Otx2, and its cells rapidly down-regulated an early transient Pax2 signal; this pattern is consistent with its reported isthmic origin and forward tangential translocation [4].
  • The torus semicircularis-the inferior colliculus homolog-expressed Otx2 in its ventricular lining exclusively, but it never expressed Pax2 [4].
  • The Otx2 expression was detected in the ventro-lateral wall of the otic anlage and could play a role in the segregation of the saccule and utricle maculae [7].
  • Moreover, CNBP and Otx2 may play roles as regulators of forebrain formation in two parallel pathways [8].
  • In the neural retina, Otx2 immunoreactivity brightly decorated the photoreceptor nuclei and extended more faintly to the outer half of the inner nuclear layer [6].

Regulatory relationships of OTX2

  • These presumably result from step-like isthmic organizer effects on Otx2-expressing midbrain neuroepithelium at different distances from a caudal FGF8 morphogen source (isthmic Fgf8-positive domain) [4].

Other interactions of OTX2

  • We propose a new nomenclature to differentiate the vesicles and constrictions observed in the avian MH domain at stage HH10 and HH20, based on the localization of the Gbx2/Otx2 common boundary [9].


  1. Implication of OTX2 in pigment epithelium determination and neural retina differentiation. Bovolenta, P., Mallamaci, A., Briata, P., Corte, G., Boncinelli, E. J. Neurosci. (1997) [Pubmed]
  2. Specification of the meso-isthmo-cerebellar region: the Otx2/Gbx2 boundary. Hidalgo-Sánchez, M., Millet, S., Bloch-Gallego, E., Alvarado-Mallart, R.M. Brain Res. Brain Res. Rev. (2005) [Pubmed]
  3. A role for the hypoblast (AVE) in the initiation of neural induction, independent of its ability to position the primitive streak. Albazerchi, A., Stern, C.D. Dev. Biol. (2007) [Pubmed]
  4. A distinct preisthmic histogenetic domain is defined by overlap of Otx2 and Pax2 gene expression in the avian caudal midbrain. Hidalgo-Sánchez, M., Martínez-de-la-Torre, M., Alvarado-Mallart, R.M., Puelles, L. J. Comp. Neurol. (2005) [Pubmed]
  5. The transcription factors Emx1 and Emx2 suppress choroid plexus development and promote neuroepithelial cell fate. von Frowein, J., Wizenmann, A., Götz, M. Dev. Biol. (2006) [Pubmed]
  6. Melatoninergic differentiation of retinal photoreceptors: activation of the chicken hydroxyindole-O-methyltransferase promoter requires a homeodomain-binding element that interacts with Otx2. Dinet, V., Girard-Naud, N., Voisin, P., Bernard, M. Exp. Eye Res. (2006) [Pubmed]
  7. Otx2, Gbx2, and Fgf8 expression patterns in the chick developing inner ear and their possible roles in otic specification and early innervation. Sánchez-Calderón, H., Martín-Partido, G., Hidalgo-Sánchez, M. Gene Expr. Patterns (2004) [Pubmed]
  8. CNBP regulates forebrain formation at organogenesis stage in chick embryos. Abe, Y., Chen, W., Huang, W., Nishino, M., Li, Y.P. Dev. Biol. (2006) [Pubmed]
  9. Comparative analysis of Otx2, Gbx2, Pax2, Fgf8 and Wnt1 gene expressions during the formation of the chick midbrain/hindbrain domain. Hidalgo-Sánchez, M., Millet, S., Simeone, A., Alvarado-Mallart, R.M. Mech. Dev. (1999) [Pubmed]
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