Homeobox protein OTX2 is a protein that in humans is encoded by the OTX2 gene.[1][2]
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Function [edit]
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.[2]
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.
Clinical significance [edit]
Mutations in OTX2 can cause eye disorders including anophthalmia and microphthalmia.[3]
It has been shown that if Otx2 is over expressed it can lead to childhood malignant brain tumors called medulloblastomas.
References [edit]
- ^ Kastury K, Druck T, Huebner K, Barletta C, Acampora D, Simeone A, Faiella A, Boncinelli E (Dec 1994). "Chromosome locations of human EMX and OTX genes". Genomics 22 (1): 41–5. doi:10.1006/geno.1994.1343. PMID 7959790.
- ^ a b "Entrez Gene: OTX2 orthodenticle homeobox 2".
- ^ Verma AS, Fitzpatrick DR (2007). "Anophthalmia and microphthalmia". Orphanet J Rare Dis 2: 47. doi:10.1186/1750-1172-2-47. PMC 2246098. PMID 18039390.
Further reading [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". Development 122 (12): 3785–97. PMID 9012500.
- Larsen KB, Lutterodt MC, Møllgård K, Møller M (July 2010). "Expression of the homeobox genes OTX2 and OTX1 in the early developing human brain". J. Histochem. Cytochem. 58 (7): 669–78. doi:10.1369/jhc.2010.955757. PMC 2889402. PMID 20354145.
- 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". Development 124 (20): 3929–41. PMID 9374391.
- Gat-Yablonski G (September 2011). "Brain development is a multi-level regulated process--the case of the OTX2 gene". Pediatr Endocrinol Rev 9 (1): 422–30. PMID 22783640.
- Béby F, Housset M, Fossat N, Le Greneur C, Flamant F, Godement P, Lamonerie T (2010). "Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration". PLoS ONE 5 (7): e11673. doi:10.1371/journal.pone.0011673. PMC 2908139. PMID 20657788.
- Hever AM, Williamson KA, van Heyningen V (2007). "Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2". Clin. Genet. 69 (6): 459–70. doi:10.1111/j.1399-0004.2006.00619.x. PMID 16712695.
- Simeone A, Acampora D, Mallamaci A et al. (1993). "A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo". EMBO J. 12 (7): 2735–47. PMC 413524. PMID 8101484.
- Nagao T, Leuzinger S, Acampora D et al. (1998). "Developmental rescue of Drosophila cephalic defects by the human Otx genes". Proc. Natl. Acad. Sci. U.S.A. 95 (7): 3737–42. Bibcode:1998PNAS...95.3737N. doi:10.1073/pnas.95.7.3737. PMC 19906. PMID 9520436.
- 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. PMID 10354480.
- 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. PMID 10372988.
- 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. PMID 10623575.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- 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. PMID 12559959.
- 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. PMID 12663655.
- Puelles E, Annino A, Tuorto F et al. (2004). "Otx2 regulates the extent, identity and fate of neuronal progenitor domains in the ventral midbrain". Development 131 (9): 2037–48. doi:10.1242/dev.01107. PMID 15105370.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Boon K, Eberhart CG, Riggins GJ (2005). "Genomic amplification of orthodenticle homologue 2 in medulloblastomas". Cancer Res. 65 (3): 703–7. PMID 15705863.
- Di C, Liao S, Adamson DC et al. (2005). "Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid". Cancer Res. 65 (3): 919–24. PMID 15705891.
- Ragge NK, Brown AG, Poloschek CM et al. (2005). "Heterozygous Mutations of OTX2 Cause Severe Ocular Malformations". Am. J. Hum. Genet. 76 (6): 1008–22. doi:10.1086/430721. PMC 1196439. PMID 15846561.
- Brunet I, Weinl C, Piper M et al. (2005). "The transcription factor Engrailed-2 guides retinal axons". Nature 438 (7064): 94–8. Bibcode:2005Natur.438...94B. doi:10.1038/nature04110. PMID 16267555.
- 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. PMID 16607563.
- Lim J, Hao T, Shaw C et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
- Heimbucher T, Murko C, Bajoghli B et al. (2007). "Gbx2 and Otx2 Interact with the WD40 Domain of Groucho/Tle Corepressors". Mol. Cell. Biol. 27 (1): 340–51. doi:10.1128/MCB.00811-06. PMC 1800652. PMID 17060451.
External links [edit]
- OTX2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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