This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and 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.
Otx-2 is necessary for retina development, retina maturation, and fate determination of photoreceptors. In the mouse, studies have shown development of the retina is regulated in a cell type- and stage-specific manner by seven Otx2 cis-regulatory modules. Three of these cis-regulatory modules, O5, O7 and O9 indicate three distinct cellular expressions of Otx2. [7] A “knockin” mouse line was generated where Crx (Otx family homeoprotein) was replaced by Otx2 and vice versa to examine the functional substitutability. It was found that Crx and Otx2 cannot be substituted in photoreceptor development. High Otx2 levels induce photoreceptor cell fate but not bipolar cell fate. Low levels of Otx2 impair bipolar cell maturation and survival.[8] Studies in the chicken confirmed a functional role for Otx2 in the determination of photoreceptors. Otx2 also represses specific retinal fates (such as subtypes of retinal ganglion and horizontal cells) of sister cells to promote the specification of photoreceptors. [9]
Clinical significance
Otx2 is expressed in the brain, ear, nose and eye, and in the case of mutations; it can lead to significant developmental abnormalities and disorders. Mutations in OTX2 can cause eye disorders including anophthalmia and microphthalmia.[10] Apart from anophthalmia and microphthalmia, other abnormalities such as aplasia of the optic nerve, hypoplasia of the optic chiasm and dysplastic optic globes have also been observed. Other defects that occur due to a mutation of the Otx2 gene include pituitary abnormalities and mental retardation. Abnormal pituitary structure and/or function seem to be the most common feature associated with Otx2 mutations.[11]
Otx2 also regulates two other genes, Lhx1 and Dkk1 that also play a role in head morphogenesis.[12] Otx2 is required during early formation of the embryo to initiate the movement of cells towards the anterior region and establish the anterior visceral endoderm. In the absence of Otx2, this movement can be impeded, which can be overcome by the expression of Dkk1, but it does not prevent the embryo from developing head truncation defects. The absence of Otx2 and the enhanced expression of Lhx1 can also lead to severe head truncation.
It has been shown that if Otx2 is over expressed it can lead to childhood malignant brain tumors called medulloblastomas.
In the mouse, the lack of Otx2 inhibits the development of the head. These 'knockout' mice that fail to form the head have gastrulation defects and die at midgestation with severe brain anomalies.
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.[14] 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 periodplasticity.[15] 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.[15] Otx2 loss-of-function experiments delayed ocular dominance plasticity by impairing the development of PV-cells.[15] 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.
Role in Embryonic Stem Cells Biology
Otx2 is a key regulator of the earliest stages of ES cell differentiation.[16][17][18] The ectopic expression of Otx2 drives ES cells into differentiation, even in the presence of the LIF cytokine. At the molecular level, Otx2 induction partially compensates the gene expression changes induced by Nanog overexpression in the absence of LIF.[19]
References
^ abcGRCh38: Ensembl release 89: ENSG00000165588 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000021848 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.
^Chan CS, Lonfat N, Zhao R, Davis AE, Li L, Wu MR, et al. (July 2020). "Cell type- and stage-specific expression of Otx2 is regulated by multiple transcription factors and cis-regulatory modules in the retina". Development. 147 (14): 1. doi:10.1242/dev.187922. PMC7406324. PMID 32631829.
^Yamamoto H, Kon T, Omori Y, Furukawa T (January 2020). "Functional and Evolutionary Diversification of Otx2 and Crx in Vertebrate Retinal Photoreceptor and Bipolar Cell Development". Cell Reports. 30 (3): 658–671.e5. doi:10.1016/j.celrep.2019.12.072. PMID 31968244.
^Ghinia Tegla MG, Buenaventura DF, Kim DY, Thakurdin C, Gonzalez KC, Emerson MM (April 2020). "OTX2 represses sister cell fate choices in the developing retina to promote photoreceptor specification". eLife. 9: 1. doi:10.7554/eLife.54279. PMC7237216. PMID 32347797.
^Verma AS, Fitzpatrick DR (November 2007). "Anophthalmia and microphthalmia". Orphanet Journal of Rare Diseases. 2: 47. doi:10.1186/1750-1172-2-47. PMC2246098. PMID 18039390.
^Schilter KF, Schneider A, Bardakjian T, Soucy JF, Tyler RC, Reis LM, Semina EV (February 2011). "OTX2 microphthalmia syndrome: four novel mutations and delineation of a phenotype". Clinical Genetics. 79 (2): 158–68. doi:10.1111/j.1399-0004.2010.01450.x. PMC3017659. PMID 20486942.
^Ip CK, Fossat N, Jones V, Lamonerie T, Tam PP (October 2014). "Head formation: OTX2 regulates Dkk1 and Lhx1 activity in the anterior mesendoderm". Development. 141 (20): 3859–67. doi:10.1242/dev.114900. PMID 25231759.
^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. Bibcode:2014PLoSO...996788Z. doi:10.1371/journal.pone.0096788. PMC4016008. PMID 24816892.
^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. S2CID 9458255.
^ abcSugiyama 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. S2CID 3110858.
^Heurtier, V., Owens, N., Gonzalez, I. et al. The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells. Nat Commun 10, 1109 (2019). https://doi.org/10.1038/s41467-019-09041-z
^Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition, Dario Acampora, Luca G. Di Giovannantonio, Antonio Simeone, Development 2013 140: 43-55; doi: 10.1242/dev.085290
^Buecker C, Srinivasan R, Wu Z, Calo E, Acampora D, Faial T, et al. (June 2014). "Reorganization of enhancer patterns in transition from naive to primed pluripotency". Cell Stem Cell. 14 (6): 838–53. doi:10.1016/j.stem.2014.04.003. PMC4491504. PMID 24905168.
^Heurtier, V., Owens, N., Gonzalez, I. et al. The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells. Nat Commun 10, 1109 (2019). https://doi.org/10.1038/s41467-019-09041-z
Further reading
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. doi:10.1242/dev.122.12.3785. 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". The Journal of Histochemistry and Cytochemistry. 58 (7): 669–78. doi:10.1369/jhc.2010.955757. PMC2889402. 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. doi:10.1242/dev.124.20.3929. PMID 9374391.
Gat-Yablonski G (September 2011). "Brain development is a multi-level regulated process--the case of the OTX2 gene". Pediatric Endocrinology Reviews. 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. Bibcode:2010PLoSO...511673B. doi:10.1371/journal.pone.0011673. PMC2908139. PMID 20657788.
Hever AM, Williamson KA, van Heyningen V (June 2006). "Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2". Clinical Genetics. 69 (6): 459–70. doi:10.1111/j.1399-0004.2006.00619.x. PMID 16712695. S2CID 5676139.
Simeone A, Acampora D, Mallamaci A, Stornaiuolo A, D'Apice MR, Nigro V, Boncinelli E (July 1993). "A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo". The EMBO Journal. 12 (7): 2735–47. doi:10.1002/j.1460-2075.1993.tb05935.x. PMC413524. PMID 8101484.
Nagao T, Leuzinger S, Acampora D, Simeone A, Finkelstein R, Reichert H, Furukubo-Tokunaga K (March 1998). "Developmental rescue of Drosophila cephalic defects by the human Otx genes". Proceedings of the National Academy of Sciences of the United States of America. 95 (7): 3737–42. Bibcode:1998PNAS...95.3737N. doi:10.1073/pnas.95.7.3737. PMC19906. PMID 9520436.
Bobola N, Briata P, Ilengo C, Rosatto N, Craft C, Corte G, Ravazzolo R (April 1999). "OTX2 homeodomain protein binds a DNA element necessary for interphotoreceptor retinoid binding protein gene expression". Mechanisms of Development. 82 (1–2): 165–9. doi:10.1016/S0925-4773(98)00162-2. PMID 10354480. S2CID 8567802.
Fong SL, Fong WB (April 1999). "Elements regulating the transcription of human interstitial retinoid-binding protein (IRBP) gene in cultured retinoblastoma cells". Current Eye Research. 18 (4): 283–91. doi:10.1076/ceyr.18.4.283.5360. PMID 10372988.
Nakano T, Murata T, Matsuo I, Aizawa S (January 2000). "OTX2 directly interacts with LIM1 and HNF-3beta". Biochemical and Biophysical Research Communications. 267 (1): 64–70. doi:10.1006/bbrc.1999.1872. PMID 10623575.
Takeda K, Yokoyama S, Yasumoto Ki, Saito H, Udono T, Takahashi K, Shibahara S (January 2003). "OTX2 regulates expression of DOPAchrome tautomerase in human retinal pigment epithelium". Biochemical and Biophysical Research Communications. 300 (4): 908–14. doi:10.1016/S0006-291X(02)02934-0. PMID 12559959.
Martínez-Morales JR, Dolez V, Rodrigo I, Zaccarini R, Leconte L, Bovolenta P, Saule S (June 2003). "OTX2 activates the molecular network underlying retina pigment epithelium differentiation". The Journal of Biological Chemistry. 278 (24): 21721–31. doi:10.1074/jbc.M301708200. PMID 12663655.
Puelles E, Annino A, Tuorto F, Usiello A, Acampora D, Czerny T, Brodski C, Ang SL, Wurst W, Simeone A (May 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.
Boon K, Eberhart CG, Riggins GJ (February 2005). "Genomic amplification of orthodenticle homologue 2 in medulloblastomas". Cancer Research. 65 (3): 703–7. doi:10.1158/0008-5472.703.65.3. PMID 15705863. S2CID 2634567.
Di C, Liao S, Adamson DC, Parrett TJ, Broderick DK, Shi Q, Lengauer C, Cummins JM, Velculescu VE, Fults DW, McLendon RE, Bigner DD, Yan H (February 2005). "Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid". Cancer Research. 65 (3): 919–24. doi:10.1158/0008-5472.919.65.3. PMID 15705891. S2CID 14049573.
Ragge NK, Brown AG, Poloschek CM, Lorenz B, Henderson RA, Clarke MP, Russell-Eggitt I, Fielder A, Gerrelli D, Martinez-Barbera JP, Ruddle P, Hurst J, Collin JR, Salt A, Cooper ST, Thompson PJ, Sisodiya SM, Williamson KA, Fitzpatrick DR, van Heyningen V, Hanson IM (June 2005). "Heterozygous mutations of OTX2 cause severe ocular malformations". American Journal of Human Genetics. 76 (6): 1008–22. doi:10.1086/430721. PMC1196439. PMID 15846561.
Brunet I, Weinl C, Piper M, Trembleau A, Volovitch M, Harris W, Prochiantz A, Holt C (November 2005). "The transcription factor Engrailed-2 guides retinal axons". Nature. 438 (7064): 94–8. Bibcode:2005Natur.438...94B. doi:10.1038/nature04110. PMC3785142. PMID 16267555.
Chatelain G, Fossat N, Brun G, Lamonerie T (July 2006). "Molecular dissection reveals decreased activity and not dominant negative effect in human OTX2 mutants". Journal of Molecular Medicine. 84 (7): 604–15. doi:10.1007/s00109-006-0048-2. PMID 16607563. S2CID 36896471.
Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (May 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. S2CID 13709685.
Heimbucher T, Murko C, Bajoghli B, Aghaallaei N, Huber A, Stebegg R, Eberhard D, Fink M, Simeone A, Czerny T (January 2007). "Gbx2 and Otx2 interact with the WD40 domain of Groucho/Tle corepressors". Molecular and Cellular Biology. 27 (1): 340–51. doi:10.1128/MCB.00811-06. PMC1800652. PMID 17060451.
orthodenticle, homeobox, homeobox, protein, otx2, protein, that, humans, encoded, otx2, gene, otx2available, structurespdbortholog, search, pdbe, rcsblist, codes2dmsidentifiersaliasesotx2, cphd6, mcops5, external, idsomim, 600037, 97451, homologene, 11026, gen. Homeobox protein OTX2 is a protein that in humans is encoded by the OTX2 gene 5 6 OTX2Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes2DMSIdentifiersAliasesOTX2 CPHD6 MCOPS5 Orthodenticle homeobox 2External IDsOMIM 600037 MGI 97451 HomoloGene 11026 GeneCards OTX2Gene location Human Chr Chromosome 14 human 1 Band14q22 3Start56 799 905 bp 1 End56 816 693 bp 1 Gene location Mouse Chr Chromosome 14 mouse 2 Band14 C1 14 25 36 cMStart48 895 134 bp 2 End48 911 276 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed insecondary oocyteretinal pigment epitheliumcerebellar hemispheretibialis anterior musclesubstantia nigrahypothalamusventral tegmental areacerebellar vermisdeltoid muscleanterior pituitaryTop expressed inpineal glandretinal pigment epitheliumlateral ventricleciliary bodyirislateral recessolfactory epitheliumsuperior colliculussacculeinner nuclear layerMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionDNA binding sequence specific DNA binding DNA binding transcription factor activity DNA binding transcription activator activity RNA polymerase II specific RNA polymerase II cis regulatory region sequence specific DNA binding protein binding eukaryotic initiation factor 4E binding DNA binding transcription factor activity RNA polymerase II specificCellular componentgrowth cone nucleus protein containing complexBiological processdopaminergic neuron differentiation regulation of transcription DNA templated positive regulation of gastrulation regulation of fibroblast growth factor receptor signaling pathway axon guidance positive regulation of transcription DNA templated multicellular organism development regulation of smoothened signaling pathway forebrain development positive regulation of embryonic development primitive streak formation midbrain development positive regulation of transcription by RNA polymerase II transcription by RNA polymerase II protein containing complex assemblySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez501518424EnsemblENSG00000165588ENSMUSG00000021848UniProtP32243P80206RefSeq mRNA NM 001270523NM 001270524NM 001270525NM 021728NM 172337NM 001286481NM 001286482NM 001286483NM 144841NM 001360225NM 001360226RefSeq protein NP 001257452NP 001257453NP 001257454NP 068374NP 758840n aLocation UCSC Chr 14 56 8 56 82 MbChr 14 48 9 48 91 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical significance 3 Role of Otx2 in Visual Plasticity 4 Role in Embryonic Stem Cells Biology 5 References 6 Further reading 7 External linksFunction EditThis gene encodes a member of the bicoid sub family of homeodomain containing transcription factors The encoded protein acts as a transcription factor and 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 Otx 2 is necessary for retina development retina maturation and fate determination of photoreceptors In the mouse studies have shown development of the retina is regulated in a cell type and stage specific manner by seven Otx2 cis regulatory modules Three of these cis regulatory modules O5 O7 and O9 indicate three distinct cellular expressions of Otx2 7 A knockin mouse line was generated where Crx Otx family homeoprotein was replaced by Otx2 and vice versa to examine the functional substitutability It was found that Crx and Otx2 cannot be substituted in photoreceptor development High Otx2 levels induce photoreceptor cell fate but not bipolar cell fate Low levels of Otx2 impair bipolar cell maturation and survival 8 Studies in the chicken confirmed a functional role for Otx2 in the determination of photoreceptors Otx2 also represses specific retinal fates such as subtypes of retinal ganglion and horizontal cells of sister cells to promote the specification of photoreceptors 9 Clinical significance EditOtx2 is expressed in the brain ear nose and eye and in the case of mutations it can lead to significant developmental abnormalities and disorders Mutations in OTX2 can cause eye disorders including anophthalmia and microphthalmia 10 Apart from anophthalmia and microphthalmia other abnormalities such as aplasia of the optic nerve hypoplasia of the optic chiasm and dysplastic optic globes have also been observed Other defects that occur due to a mutation of the Otx2 gene include pituitary abnormalities and mental retardation Abnormal pituitary structure and or function seem to be the most common feature associated with Otx2 mutations 11 Otx2 also regulates two other genes Lhx1 and Dkk1 that also play a role in head morphogenesis 12 Otx2 is required during early formation of the embryo to initiate the movement of cells towards the anterior region and establish the anterior visceral endoderm In the absence of Otx2 this movement can be impeded which can be overcome by the expression of Dkk1 but it does not prevent the embryo from developing head truncation defects The absence of Otx2 and the enhanced expression of Lhx1 can also lead to severe head truncation 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 13 In the mouse the lack of Otx2 inhibits the development of the head These knockout mice that fail to form the head have gastrulation defects and die at midgestation with severe brain anomalies Role of Otx2 in Visual Plasticity EditRecent research has identified the homeoprotein Otx2 as a possible molecular messenger that is necessary for experience driven visual plasticity during the critical period 14 Initially involved in embryonic head formation Otx2 is re expressed during the critical period of rats gt P23 and regulates the maturation of parvalbumin expressing GABAergic interneurons PV cells which control the onset of critical period plasticity 15 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 15 Otx2 loss of function experiments delayed ocular dominance plasticity by impairing the development of PV cells 15 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 Role in Embryonic Stem Cells Biology EditOtx2 is a key regulator of the earliest stages of ES cell differentiation 16 17 18 The ectopic expression of Otx2 drives ES cells into differentiation even in the presence of the LIF cytokine At the molecular level Otx2 induction partially compensates the gene expression changes induced by Nanog overexpression in the absence of LIF 19 References Edit a b c GRCh38 Ensembl release 89 ENSG00000165588 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000021848 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine 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 a b Entrez Gene OTX2 orthodenticle homeobox 2 Chan CS Lonfat N Zhao R Davis AE Li L Wu MR et al July 2020 Cell type and stage specific expression of Otx2 is regulated by multiple transcription factors and cis regulatory modules in the retina Development 147 14 1 doi 10 1242 dev 187922 PMC 7406324 PMID 32631829 Yamamoto H Kon T Omori Y Furukawa T January 2020 Functional and Evolutionary Diversification of Otx2 and Crx in Vertebrate Retinal Photoreceptor and Bipolar Cell Development Cell Reports 30 3 658 671 e5 doi 10 1016 j celrep 2019 12 072 PMID 31968244 Ghinia Tegla MG Buenaventura DF Kim DY Thakurdin C Gonzalez KC Emerson MM April 2020 OTX2 represses sister cell fate choices in the developing retina to promote photoreceptor specification eLife 9 1 doi 10 7554 eLife 54279 PMC 7237216 PMID 32347797 Verma AS Fitzpatrick DR November 2007 Anophthalmia and microphthalmia Orphanet Journal of Rare Diseases 2 47 doi 10 1186 1750 1172 2 47 PMC 2246098 PMID 18039390 Schilter KF Schneider A Bardakjian T Soucy JF Tyler RC Reis LM Semina EV February 2011 OTX2 microphthalmia syndrome four novel mutations and delineation of a phenotype Clinical Genetics 79 2 158 68 doi 10 1111 j 1399 0004 2010 01450 x PMC 3017659 PMID 20486942 Ip CK Fossat N Jones V Lamonerie T Tam PP October 2014 Head formation OTX2 regulates Dkk1 and Lhx1 activity in the anterior mesendoderm Development 141 20 3859 67 doi 10 1242 dev 114900 PMID 25231759 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 Bibcode 2014PLoSO 996788Z doi 10 1371 journal pone 0096788 PMC 4016008 PMID 24816892 Sugiyama S Prochiantz A Hensch TK April 2009 From brain formation to plasticity insights on Otx2 homeoprotein Development Growth amp Differentiation 51 3 369 77 doi 10 1111 j 1440 169X 2009 01093 x PMID 19298552 S2CID 9458255 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 S2CID 3110858 Heurtier V Owens N Gonzalez I et al The molecular logic of Nanog induced self renewal in mouse embryonic stem cells Nat Commun 10 1109 2019 https doi org 10 1038 s41467 019 09041 z Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition Dario Acampora Luca G Di Giovannantonio Antonio Simeone Development 2013 140 43 55 doi 10 1242 dev 085290 Buecker C Srinivasan R Wu Z Calo E Acampora D Faial T et al June 2014 Reorganization of enhancer patterns in transition from naive to primed pluripotency Cell Stem Cell 14 6 838 53 doi 10 1016 j stem 2014 04 003 PMC 4491504 PMID 24905168 Heurtier V Owens N Gonzalez I et al The molecular logic of Nanog induced self renewal in mouse embryonic stem cells Nat Commun 10 1109 2019 https doi org 10 1038 s41467 019 09041 zFurther reading EditMillet 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 doi 10 1242 dev 122 12 3785 PMID 9012500 Larsen KB Lutterodt MC Mollgard K Moller M July 2010 Expression of the homeobox genes OTX2 and OTX1 in the early developing human brain The Journal of Histochemistry and Cytochemistry 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 doi 10 1242 dev 124 20 3929 PMID 9374391 Gat Yablonski G September 2011 Brain development is a multi level regulated process the case of the OTX2 gene Pediatric Endocrinology Reviews 9 1 422 30 PMID 22783640 Beby 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 Bibcode 2010PLoSO 511673B doi 10 1371 journal pone 0011673 PMC 2908139 PMID 20657788 Hever AM Williamson KA van Heyningen V June 2006 Developmental malformations of the eye the role of PAX6 SOX2 and OTX2 Clinical Genetics 69 6 459 70 doi 10 1111 j 1399 0004 2006 00619 x PMID 16712695 S2CID 5676139 Simeone A Acampora D Mallamaci A Stornaiuolo A D Apice MR Nigro V Boncinelli E July 1993 A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo The EMBO Journal 12 7 2735 47 doi 10 1002 j 1460 2075 1993 tb05935 x PMC 413524 PMID 8101484 Nagao T Leuzinger S Acampora D Simeone A Finkelstein R Reichert H Furukubo Tokunaga K March 1998 Developmental rescue of Drosophila cephalic defects by the human Otx genes Proceedings of the National Academy of Sciences of the United States of America 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 Rosatto N Craft C Corte G Ravazzolo R April 1999 OTX2 homeodomain protein binds a DNA element necessary for interphotoreceptor retinoid binding protein gene expression Mechanisms of Development 82 1 2 165 9 doi 10 1016 S0925 4773 98 00162 2 PMID 10354480 S2CID 8567802 Fong SL Fong WB April 1999 Elements regulating the transcription of human interstitial retinoid binding protein IRBP gene in cultured retinoblastoma cells Current Eye Research 18 4 283 91 doi 10 1076 ceyr 18 4 283 5360 PMID 10372988 Nakano T Murata T Matsuo I Aizawa S January 2000 OTX2 directly interacts with LIM1 and HNF 3beta Biochemical and Biophysical Research Communications 267 1 64 70 doi 10 1006 bbrc 1999 1872 PMID 10623575 Takeda K Yokoyama S Yasumoto Ki Saito H Udono T Takahashi K Shibahara S January 2003 OTX2 regulates expression of DOPAchrome tautomerase in human retinal pigment epithelium Biochemical and Biophysical Research Communications 300 4 908 14 doi 10 1016 S0006 291X 02 02934 0 PMID 12559959 Martinez Morales JR Dolez V Rodrigo I Zaccarini R Leconte L Bovolenta P Saule S June 2003 OTX2 activates the molecular network underlying retina pigment epithelium differentiation The Journal of Biological Chemistry 278 24 21721 31 doi 10 1074 jbc M301708200 PMID 12663655 Puelles E Annino A Tuorto F Usiello A Acampora D Czerny T Brodski C Ang SL Wurst W Simeone A May 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 Boon K Eberhart CG Riggins GJ February 2005 Genomic amplification of orthodenticle homologue 2 in medulloblastomas Cancer Research 65 3 703 7 doi 10 1158 0008 5472 703 65 3 PMID 15705863 S2CID 2634567 Di C Liao S Adamson DC Parrett TJ Broderick DK Shi Q Lengauer C Cummins JM Velculescu VE Fults DW McLendon RE Bigner DD Yan H February 2005 Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all trans retinoic acid Cancer Research 65 3 919 24 doi 10 1158 0008 5472 919 65 3 PMID 15705891 S2CID 14049573 Ragge NK Brown AG Poloschek CM Lorenz B Henderson RA Clarke MP Russell Eggitt I Fielder A Gerrelli D Martinez Barbera JP Ruddle P Hurst J Collin JR Salt A Cooper ST Thompson PJ Sisodiya SM Williamson KA Fitzpatrick DR van Heyningen V Hanson IM June 2005 Heterozygous mutations of OTX2 cause severe ocular malformations American Journal of Human Genetics 76 6 1008 22 doi 10 1086 430721 PMC 1196439 PMID 15846561 Brunet I Weinl C Piper M Trembleau A Volovitch M Harris W Prochiantz A Holt C November 2005 The transcription factor Engrailed 2 guides retinal axons Nature 438 7064 94 8 Bibcode 2005Natur 438 94B doi 10 1038 nature04110 PMC 3785142 PMID 16267555 Chatelain G Fossat N Brun G Lamonerie T July 2006 Molecular dissection reveals decreased activity and not dominant negative effect in human OTX2 mutants Journal of Molecular Medicine 84 7 604 15 doi 10 1007 s00109 006 0048 2 PMID 16607563 S2CID 36896471 Lim J Hao T Shaw C Patel AJ Szabo G Rual JF Fisk CJ Li N Smolyar A Hill DE Barabasi AL Vidal M Zoghbi HY May 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 S2CID 13709685 Heimbucher T Murko C Bajoghli B Aghaallaei N Huber A Stebegg R Eberhard D Fink M Simeone A Czerny T January 2007 Gbx2 and Otx2 interact with the WD40 domain of Groucho Tle corepressors Molecular and Cellular Biology 27 1 340 51 doi 10 1128 MCB 00811 06 PMC 1800652 PMID 17060451 External links EditOTX2 protein human at the US National Library of Medicine Medical Subject Headings MeSH Overview of all the structural information available in the PDB for UniProt P80206 Mouse Homeobox protein OTX2 at the PDBe KB This article incorporates text from the United States National Library of Medicine which is in the public domain Retrieved from https en wikipedia org w index php title Orthodenticle homeobox 2 amp oldid 1136370034, wikipedia, wiki, book, books, library,
