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.
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 insuring 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.
^Zielinski, D; Markus, B; Sheikh, M; Gymrek, M; Chu, C; Zaks, M; Srinivasan, B; Hoffman, J. D.; Aizenbud, D; Erlich, Y (2014). "OTX2 Duplication is Implicated in Hemifacial Microsomia". PLoS ONE9 (5): e96788. doi:10.1371/journal.pone.0096788. PMID24816892.edit
Millet S, Bloch-Gallego E, Simeone A, Alvarado-Mallart RM (December 1996). "The caudal limit of Otx2 gene expression as a marker of the midbrain/hindbrain boundary: a study using in situ hybridisation and chick/quail homotopic grafts". Development122 (12): 3785–97. PMID9012500.
Kimura C, Takeda N, Suzuki M, Oshimura M, Aizawa S, Matsuo I (October 1997). "Cis-acting elements conserved between mouse and pufferfish Otx2 genes govern the expression in mesencephalic neural crest cells". Development124 (20): 3929–41. PMID9374391.
Gat-Yablonski G (September 2011). "Brain development is a multi-level regulated process--the case of the OTX2 gene". Pediatr Endocrinol Rev9 (1): 422–30. PMID22783640.
Bobola N, Briata P, Ilengo C et al. (1999). "OTX2 homeodomain protein binds a DNA element necessary for interphotoreceptor retinoid binding protein gene expression". Mech. Dev.82 (1–2): 165–9. doi:10.1016/S0925-4773(98)00162-2. PMID10354480.
Fong SL, Fong WB (1999). "Elements regulating the transcription of human interstitial retinoid-binding protein (IRBP) gene in cultured retinoblastoma cells". Curr. Eye Res.18 (4): 283–91. doi:10.1076/ceyr.18.4.283.5360. PMID10372988.
Nakano T, Murata T, Matsuo I, Aizawa S (2000). "OTX2 directly interacts with LIM1 and HNF-3beta". Biochem. Biophys. Res. Commun.267 (1): 64–70. doi:10.1006/bbrc.1999.1872. PMID10623575.
Takeda K, Yokoyama S, Yasumoto K et al. (2003). "OTX2 regulates expression of DOPAchrome tautomerase in human retinal pigment epithelium". Biochem. Biophys. Res. Commun.300 (4): 908–14. doi:10.1016/S0006-291X(02)02934-0. PMID12559959.
Martínez-Morales JR, Dolez V, Rodrigo I et al. (2003). "OTX2 activates the molecular network underlying retina pigment epithelium differentiation". J. Biol. Chem.278 (24): 21721–31. doi:10.1074/jbc.M301708200. PMID12663655.
Puelles E, Annino A, Tuorto F et al. (2004). "Otx2 regulates the extent, identity and fate of neuronal progenitor domains in the ventral midbrain". Development131 (9): 2037–48. doi:10.1242/dev.01107. PMID15105370.
Chatelain G, Fossat N, Brun G, Lamonerie T (2007). "Molecular dissection reveals decreased activity and not dominant negative effect in human OTX2 mutants". J. Mol. Med.84 (7): 604–15. doi:10.1007/s00109-006-0048-2. PMID16607563.
Lim J, Hao T, Shaw C et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID16713569.