RefSeq (protein)



Location (UCSC) Chr 14: 56.8 – 56.81 Mb Chr 14: 48.66 – 48.67 Mb PubMed search [3] [4] Wikidata
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Homeobox protein OTX2 is a protein that in humans is encoded by the OTX2 gene.[5][6]


This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and may play a role in brain and sensory organ development. A similar protein in mice is required for proper forebrain development. Two transcript variants encoding distinct isoforms have been identified for this gene. Other alternative splice variants may exist, but their full length sequences have not been determined.[6]

Otx2 is a group of homeobox genes that are typically described as a head organizer in the primitive streak stage of embryonic development. Otx2, which is an encoded protein that plays the role of a transcription factor, has also been shown to be involved in the regional patterning of the midbrain and forebrain. This group of genes demonstrates later in progression to have an influence on the formation of the sensory organs, pituitary gland, pineal gland, inner ear, eye and optic nerve. Otx2 not only has a prominent role in developing this area but also aids in ensuring that the retina and brain stay intact. This group of genes has a huge role in development and if it is expressed incorrectly it can have detrimental effects on the fetus. Otx2 mutations have also been associated with seizures, developmental delays, short stature, structural abnormalities of the pituitary gland, and an early onset of degeneration of the retina. A “knockout” model on the group of Otx2 genes has been performed to see what effects it would have on the adult retina. It was found that without the Otx2 gene expression there was slow degeneration of photoreceptor cells in this area. Thus, proving that the homeobox genes of Otx2 are essential in forming a viable embryo.

Clinical significance

Mutations in OTX2 can cause eye disorders including anophthalmia and microphthalmia.[7]

It has been shown that if Otx2 is over expressed it can lead to childhood malignant brain tumors called medulloblastomas.

Duplication of OTX2 is involved in the pathogenesis of Hemifacial Microsomia .[8]

Role of Otx2 in Visual Plasticity

Recent research has identified the homeoprotein Otx2 as a possible molecular ‘messenger’ that is necessary for experience-driven visual plasticity during the critical period.[9] Initially involved in embryonic head formation, Otx2 is re-expressed during the critical period of rats (>P23) and regulates the maturation of parvalbumin-expressing GABAergic interneurons (PV-cells), which control the onset of critical period plasticity.[10] Dark-rearing from birth and binocular enucleation of rats resulted in decreased expression of PV-cells and Otx2, which suggests that these proteins are visually experience-driven.[10] Otx2 loss-of-function experiments delayed ocular dominance plasticity by impairing the development of PV-cells.[10] Research into Otx2 and visual plasticity during the critical period is of particular interest to the study of developmental abnormalities such as amblyopia. More research must be conducted to determine if Otx2 could be utilized for therapeutic recovery of visual plasticity to aid some amblyopic patients.


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000165588 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021848 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Kastury K, Druck T, Huebner K, Barletta C, Acampora D, Simeone A, Faiella A, Boncinelli E (July 1994). "Chromosome locations of human EMX and OTX genes". Genomics. 22 (1): 41–5. doi:10.1006/geno.1994.1343. PMID 7959790. 
  6. ^ a b "Entrez Gene: OTX2 orthodenticle homeobox 2". 
  7. ^ Verma AS, Fitzpatrick DR (2007). "Anophthalmia and microphthalmia". Orphanet Journal of Rare Diseases. 2: 47. doi:10.1186/1750-1172-2-47. PMC 2246098Freely accessible. PMID 18039390. 
  8. ^ Zielinski D, Markus B, Sheikh M, Gymrek M, Chu C, Zaks M, Srinivasan B, Hoffman JD, Aizenbud D, Erlich Y (2014). "OTX2 duplication is implicated in hemifacial microsomia". PLoS One. 9 (5): e96788. doi:10.1371/journal.pone.0096788. PMC 4016008Freely accessible. PMID 24816892. 
  9. ^ Sugiyama S, Prochiantz A, Hensch TK (April 2009). "From brain formation to plasticity: insights on Otx2 homeoprotein". Development, Growth & Differentiation. 51 (3): 369–77. doi:10.1111/j.1440-169X.2009.01093.x. PMID 19298552. 
  10. ^ a b c Sugiyama S, Di Nardo AA, Aizawa S, Matsuo I, Volovitch M, Prochiantz A, Hensch TK (August 2008). "Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity". Cell. 134 (3): 508–20. doi:10.1016/j.cell.2008.05.054. PMID 18692473. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.