Gene Symbol: Otx1
Description: orthodenticle homeobox 1
Alias: A730044F23Rik, homeobox protein OTX1, orthodenticle homolog 1
Species: mouse
Products:     Otx1

Top Publications

  1. Martinez Morales J, Signore M, Acampora D, Simeone A, Bovolenta P. Otx genes are required for tissue specification in the developing eye. Development. 2001;128:2019-30 pubmed
    ..Previous data suggest that both Otx1 and Otx2 might contribute to the establishment of the different eye territories...
  2. Bok J, Dolson D, Hill P, Ruther U, Epstein D, Wu D. Opposing gradients of Gli repressor and activators mediate Shh signaling along the dorsoventral axis of the inner ear. Development. 2007;134:1713-22 pubmed
    ..Taken together, our data suggest that reciprocal gradients of GliA and GliR mediate the responses to Shh signaling along the dorsoventral axis of the inner ear...
  3. Tian E, Kimura C, Takeda N, Aizawa S, Matsuo I. Otx2 is required to respond to signals from anterior neural ridge for forebrain specification. Dev Biol. 2002;242:204-23 pubmed
    ..These results further suggest that Otx2 dosage may be crucial in the neural plate with respect to response to inductive signals primarily from the ANR for forebrain specification. ..
  4. Weimann J, Zhang Y, Levin M, Devine W, Brulet P, McConnell S. Cortical neurons require Otx1 for the refinement of exuberant axonal projections to subcortical targets. Neuron. 1999;24:819-31 pubmed
    ..The homeodomain transcription factor Otx1 is expressed in early-generated neurons of the developing cerebral cortex...
  5. Resch K, Korthaus D, Wedemeyer N, Lengeling A, Ronsiek M, Thiel C, et al. Homology between human chromosome 2p13.3 and the wobbler critical region on mouse chromosome 11: comparative high-resolution mapping of STS and EST loci on YAC/BAC contigs. Mamm Genome. 1998;9:893-8 pubmed
    ..11. The maps comprise several known genes, MEIS1/Meis1, RAB1a/Rab1a, MDH1/Mor2, OTX1/Otx1, and REL on human 2p13...
  6. Acampora D, Mazan S, Avantaggiato V, Barone P, Tuorto F, Lallemand Y, et al. Epilepsy and brain abnormalities in mice lacking the Otx1 gene. Nat Genet. 1996;14:218-22 pubmed
    ..We have previously cloned and characterized the murine Otx1 gene, which is related to orthodenticle (otd), a homeobox-containing gene required for Drosophila head development...
  7. Fotaki V, Smith R, Pratt T, Price D. Foxg1 is required to limit the formation of ciliary margin tissue and Wnt/?-catenin signalling in the developing nasal retina of the mouse. Dev Biol. 2013;380:299-313 pubmed publisher
    ..Our results reveal a new role of Foxg1 in limiting CM development in the nasal peripheral retina and add a new molecular player in the developmental network involved in CM specification. ..
  8. Gamse J, Shen Y, Thisse C, Thisse B, Raymond P, Halpern M, et al. Otx5 regulates genes that show circadian expression in the zebrafish pineal complex. Nat Genet. 2002;30:117-21 pubmed
    ..Our results indicate that Otx5 rather than Crx regulates genes that show circadian expression in the zebrafish pineal complex. ..
  9. Matsushima D, Heavner W, Pevny L. Combinatorial regulation of optic cup progenitor cell fate by SOX2 and PAX6. Development. 2011;138:443-54 pubmed publisher
    ..Collectively, these results demonstrate that precise regulation of the ratio of SOX2 to PAX6 is necessary to ensure accurate progenitor cell specification, and place SOX2 as a decisive factor of neural competence in the retina. ..

More Information


  1. Acampora D, Mazan S, Lallemand Y, Avantaggiato V, Maury M, Simeone A, et al. Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification during gastrulation. Development. 1995;121:3279-90 pubmed
  2. Riccomagno M, Martinu L, Mulheisen M, Wu D, Epstein D. Specification of the mammalian cochlea is dependent on Sonic hedgehog. Genes Dev. 2002;16:2365-78 pubmed
    ..back to alterations in the expression of a number of genes involved in cell fate specification including Pax2, Otx1, Otx2, Tbx1, and Ngn1...
  3. Liu H, Xu S, Wang Y, Mazerolle C, Thurig S, Coles B, et al. Ciliary margin transdifferentiation from neural retina is controlled by canonical Wnt signaling. Dev Biol. 2007;308:54-67 pubmed
    ..with lithium (Li(+)) treatment in retinal explants in vitro induced the ectopic expression of the CM markers Otx1 and Msx1...
  4. Hanashima C, Li S, Shen L, Lai E, Fishell G. Foxg1 suppresses early cortical cell fate. Science. 2004;303:56-9 pubmed
    ..Hence, the competence to generate the earliest born neurons during later cortical development is actively suppressed but not lost. ..
  5. Simeone A, Acampora D, Mallamaci A, Stornaiuolo A, D Apice M, Nigro V, et al. A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. EMBO J. 1993;12:2735-47 pubmed
    We studied the expression of two vertebrate homeobox genes, Otx1 and Otx2, related to orthodenticle, a gene expressed in the developing head of Drosophila...
  6. Frantz G, Weimann J, Levin M, McConnell S. Otx1 and Otx2 define layers and regions in developing cerebral cortex and cerebellum. J Neurosci. 1994;14:5725-40 pubmed
    ..formation in layered regions of the CNS, we have characterized the patterns of expression of two homeodomain genes, Otx1 and Otx2, by in situ hybridization during embryonic and postnatal development in the rat...
  7. Kurokawa D, Kiyonari H, Nakayama R, Kimura Yoshida C, Matsuo I, Aizawa S. Regulation of Otx2 expression and its functions in mouse forebrain and midbrain. Development. 2004;131:3319-31 pubmed
    ..and diencephalic regions was differentially regulated in a dose-dependent manner by the cooperation between Otx1 and Otx2 under FM and FM2 enhancers: the more caudal the structure the higher the OTX dose requirement. At E10...
  8. Horsford D, Nguyen M, Sellar G, Kothary R, Arnheiter H, McInnes R. Chx10 repression of Mitf is required for the maintenance of mammalian neuroretinal identity. Development. 2005;132:177-87 pubmed
    ..We demonstrate that the repression of Mitf by FGF is Chx10 dependent, indicating that FGF, Chx10 and Mitf are components of a pathway that determines and maintains the identity of the NR. ..
  9. Raft S, Nowotschin S, Liao J, Morrow B. Suppression of neural fate and control of inner ear morphogenesis by Tbx1. Development. 2004;131:1801-12 pubmed
    ..and is required for induction or proper patterning of gene expression related to sensory organ morphogenesis (Otx1 and Bmp4, respectively)...
  10. Acampora D, Avantaggiato V, Tuorto F, Briata P, Corte G, Simeone A. Visceral endoderm-restricted translation of Otx1 mediates recovery of Otx2 requirements for specification of anterior neural plate and normal gastrulation. Development. 1998;125:5091-104 pubmed
    b>Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, contribute to brain morphogenesis...
  11. Zhao S, Chen Q, Hung F, Overbeek P. BMP signaling is required for development of the ciliary body. Development. 2002;129:4435-42 pubmed
    ..These results indicate that BMP signaling is required for development of the ciliary body and may also play a role in regulation of neuronal differentiation in the developing eye. ..
  12. Pantò M, Zappala A, Tuorto F, Cicirata F. Role of the Otx1 gene in cell differentiation of mammalian cortex. Eur J Neurosci. 2004;19:2893-902 pubmed
    This study analyses by immunohistochemical methods the effects of the deletion of the Otx1 gene on 12 areas of the cerebral cortex and on neurons expressing Ca-binding proteins (CaBP), such as parvalbumin (Pv) and calbindin-D28K (Cb)...
  13. Germot A, Lecointre G, Plouhinec J, Le Mentec C, Girardot F, Mazan S. Structural evolution of Otx genes in craniates. Mol Biol Evol. 2001;18:1668-78 pubmed
    ..Two of the three genes identified in each of these species belong to the Otx1 and Otx2 orthology classes previously characterized in osteichthyans...
  14. Hägglund A, Jones I, Carlsson L. A novel mouse model of anterior segment dysgenesis (ASD): conditional deletion of Tsc1 disrupts ciliary body and iris development. Dis Model Mech. 2017;10:245-257 pubmed publisher
  15. Beatty J, Laughlin R. Genomic regulation of natural variation in cortical and noncortical brain volume. BMC Neurosci. 2006;7:16 pubmed
    ..Evidence for a candidate gene modulating neocortical volume was much weaker, but Otx1 deserves further consideration.
  16. Foucher I, Mione M, Simeone A, Acampora D, Bally Cuif L, Houart C. Differentiation of cerebellar cell identities in absence of Fgf signalling in zebrafish Otx morphants. Development. 2006;133:1891-900 pubmed
    ..This maintenance is enough to allow cerebellar differentiation. ..
  17. Tarabykin V, Stoykova A, Usman N, Gruss P. Cortical upper layer neurons derive from the subventricular zone as indicated by Svet1 gene expression. Development. 2001;128:1983-93 pubmed
    ..The VZ is marked by the expression of the Otx1 gene...
  18. Monaghan A, Grau E, Bock D, Schutz G. The mouse homolog of the orphan nuclear receptor tailless is expressed in the developing forebrain. Development. 1995;121:839-53 pubmed
    ..those of other forebrain markers, including distal-less (Dlx1), brain factor 1 (BF1), and the orthodenticle genes (Otx1 and Otx2)...
  19. Alldredge A, Fuhrmann S. Loss of Axin2 Causes Ocular Defects During Mouse Eye Development. Invest Ophthalmol Vis Sci. 2016;57:5253-5262 pubmed publisher
    ..Our results reveal a critical role for Axin2 during ocular development, likely by restricting the activity of the Wnt/?-catenin pathway. ..
  20. Heavner W, Andoniadou C, Pevny L. Establishment of the neurogenic boundary of the mouse retina requires cooperation of SOX2 and WNT signaling. Neural Dev. 2014;9:27 pubmed publisher
  21. Acampora D, Avantaggiato V, Tuorto F, Barone P, Perera M, Choo D, et al. Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes. Development. 1999;126:1417-26 pubmed
    b>Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, show a limited amino acid sequence divergence...
  22. Finkelstein R, Boncinelli E. From fly head to mammalian forebrain: the story of otd and Otx. Trends Genet. 1994;10:310-5 pubmed
    ..These studies suggest that this domain is specified according to a genetic paradigm that is different from that governing trunk development, and are also beginning to provide insights into the structures that underlie the rostral brain. ..
  23. Zou C, Levine E. Vsx2 controls eye organogenesis and retinal progenitor identity via homeodomain and non-homeodomain residues required for high affinity DNA binding. PLoS Genet. 2012;8:e1002924 pubmed publisher
    ..This occurred through a cryptic transcriptional feedback loop involving the transcription factors Mitf and Otx1 and the Cdk inhibitor p27(Kip1)...
  24. Brodski C, Weisenhorn D, Signore M, Sillaber I, Oesterheld M, Broccoli V, et al. Location and size of dopaminergic and serotonergic cell populations are controlled by the position of the midbrain-hindbrain organizer. J Neurosci. 2003;23:4199-207 pubmed
    ..In addition, our data suggest that the position of the MHO during embryogenesis can modulate adult locomotor activity. ..
  25. Vasistha N, García Moreno F, Arora S, Cheung A, Arnold S, Robertson E, et al. Cortical and Clonal Contribution of Tbr2 Expressing Progenitors in the Developing Mouse Brain. Cereb Cortex. 2015;25:3290-302 pubmed publisher
    ..Our study also describes extracortical contributions from Tbr2+ progenitors to the lateral olfactory tract and ventromedial hypothalamic nucleus. ..
  26. Qiu M, Anderson S, Chen S, Meneses J, Hevner R, Kuwana E, et al. Mutation of the Emx-1 homeobox gene disrupts the corpus callosum. Dev Biol. 1996;178:174-8 pubmed
    ..Heterozygotes show partial penetrance for the corpus callosum abnormality. The histology and various molecular properties of the cerebral cortex appear normal in the mutant mice. ..
  27. DeGregorio L, Manenti G, Simeone A, Dragani T. Genetic mapping of the homeobox-containing gene Otx1 gene on mouse chromosome 11. Mamm Genome. 1996;7:241 pubmed
  28. Sharman A, Brand M. Evolution and homology of the nervous system: cross-phylum rescues of otd/Otx genes. Trends Genet. 1998;14:211-4 pubmed
  29. Causeret F, Ensini M, Teissier A, Kessaris N, Richardson W, Lucas de Couville T, et al. Dbx1-expressing cells are necessary for the survival of the mammalian anterior neural and craniofacial structures. PLoS ONE. 2011;6:e19367 pubmed publisher
    ..Our results demonstrate that dbx1-expressing cells have a unique function during head development, notably by controlling cell survival in a non cell-autonomous manner. ..
  30. Acampora D, Gulisano M, Simeone A. Genetic and molecular roles of Otx homeodomain proteins in head development. Gene. 2000;246:23-35 pubmed
    ..Among them, transcription factors belonging to the orthodenticle family (Otx1, Otx2) play an important role during early and later events required for proper brain development...
  31. Hwang C, Simeone A, Lai E, Wu D. Foxg1 is required for proper separation and formation of sensory cristae during inner ear development. Dev Dyn. 2009;238:2725-34 pubmed publisher
    ..Our genetic fate-mapping analyses indicate an improper separation between anterior and lateral cristae in Foxg1(-/-) mutants. Our data further suggest that a function of Foxg1 in the inner ear is to restrict sensory fate. ..
  32. Michibata H, Okuno T, Konishi N, Wakimoto K, Kyono K, Aoki K, et al. Inhibition of mouse GPM6A expression leads to decreased differentiation of neurons derived from mouse embryonic stem cells. Stem Cells Dev. 2008;17:641-51 pubmed publisher
    ..showed that expression of shRNA against GPM6A markedly reduced the expression of neuroectodermal-associated genes (OTX1, Lmx1b, En1, Pax2, Pax5, Sox1, Sox2, and Wnt1), and also the number of neural stem cells (NSC) derived from ..
  33. Santagata S, Maire C, Idbaih A, Geffers L, Correll M, Holton K, et al. CRX is a diagnostic marker of retinal and pineal lineage tumors. PLoS ONE. 2009;4:e7932 pubmed publisher
    ..They also identify CRX as a sensitive and specific clinical marker and a potential lineage dependent therapeutic target in retinoblastoma and pineoblastoma. ..
  34. Zhang Y, Burgess D, Overbeek P, Govindarajan V. Dominant inhibition of lens placode formation in mice. Dev Biol. 2008;323:53-63 pubmed publisher
    ..In addition, our results also suggest that the lens cells of the surface ectoderm may be critical for the proper differentiation of the corneal epithelium. ..
  35. Dohmoto A, Shimizu K, Asada Y, Maeda T. Quantitative trait loci on chromosomes 10 and 11 influencing mandible size of SMXA RI mouse strains. J Dent Res. 2002;81:501-4 pubmed
    ..These results suggest that the major gene(s) responsible for mandible length are located in these regions. ..
  36. Boncinelli E, Gulisano M, Broccoli V. Emx and Otx homeobox genes in the developing mouse brain. J Neurobiol. 1993;24:1356-66 pubmed
    ..Two of these genes, Emx1 and Emx2, are related to empty spiracles, and two genes, termed Otx1 and Otx2, are related to orthodenticle...
  37. Sancini G, Franceschetti S, Lavazza T, Panzica F, Cipelletti B, Frassoni C, et al. Potentially epileptogenic dysfunction of cortical NMDA- and GABA-mediated neurotransmission in Otx1-/- mice. Eur J Neurosci. 2001;14:1065-74 pubmed
    Knockout Otx1 mice present a microcephalic phenotype mainly due to reduced deep neocortical layers and spontaneous recurrent seizures...
  38. Suda Y, Hossain Z, Kobayashi C, Hatano O, Yoshida M, Matsuo I, et al. Emx2 directs the development of diencephalon in cooperation with Otx2. Development. 2001;128:2433-50 pubmed
    ..Consequently, development of the dorsal and ventral thalamus and anterior pretectum requires cooperation between Emx2 and Otx2, whereas Emx2 expression is incompatible with development of the commissural region of the pretectum. ..
  39. Boyl P, Signore M, Annino A, Barbera J, Acampora D, Simeone A. Otx genes in the development and evolution of the vertebrate brain. Int J Dev Neurosci. 2001;19:353-63 pubmed
    ..Among these, the orthodenticle group, including the Drosophila orthodenticle (otd) and the vertebrate Otx1 and Otx2 genes, is mostly involved in fundamental processes of anterior neural patterning...
  40. Morsli H, Tuorto F, Choo D, Postiglione M, Simeone A, Wu D. Otx1 and Otx2 activities are required for the normal development of the mouse inner ear. Development. 1999;126:2335-43 pubmed
    The Otx1 and Otx2 genes are two murine orthologues of the Orthodenticle (Otd) gene in Drosophila. In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear...
  41. Suda Y, Matsuo I, Kuratani S, Aizawa S. Otx1 function overlaps with Otx2 in development of mouse forebrain and midbrain. Genes Cells. 1996;1:1031-44 pubmed
    ..Defects were characteristic in the most anterior and posterior regions of Otx2 expression where Otx1, another mouse cognate of orthodenticle, is not or weakly expressed...
  42. Avantaggiato V, Pandolfi P, Ruthardt M, Hawe N, Acampora D, Pelicci P, et al. Developmental analysis of murine Promyelocyte Leukemia Zinc Finger (PLZF) gene expression: implications for the neuromeric model of the forebrain organization. J Neurosci. 1995;15:4927-42 pubmed
  43. Horn Z, Papachristou P, Shariatmadari M, Peyronnet J, Eriksson B, Ringstedt T. Wnt7a overexpression delays beta-tubulin III expression in transgenic mouse embryos. Brain Res. 2007;1130:67-72 pubmed
    ..Our results corroborate previous studies using HA-Wnt7a, and suggest a critical role for Wnt7a in control of neuronal progenitor maturation. ..
  44. Kanzler B, Viallet J, Le Mouellic H, Boncinelli E, Duboule D, Dhouailly D. Differential expression of two different homeobox gene families during mouse tegument morphogenesis. Int J Dev Biol. 1994;38:633-40 pubmed
    ..The first family included the Otx1 and Otx2 genes, both related to the orthodenticle Drosophila gene and the second was represented by four members of ..
  45. Sigulinsky C, German M, Leung A, Clark A, Yun S, Levine E. Genetic chimeras reveal the autonomy requirements for Vsx2 in embryonic retinal progenitor cells. Neural Dev. 2015;10:12 pubmed publisher
    ..These findings highlight the complexity of Vsx2 function during retinal development and provide a framework for identifying the molecular mechanisms mediating these functions. ..
  46. Boncinelli E, Gulisano M, Pannese M. Conserved homeobox genes in the developing brain. C R Acad Sci III. 1993;316:972-84 pubmed
    ..to two Drosophila genes expressed in the developing head of the fly: Emx1 and Emx2, related to empty spiracles and Otx1 and Otx2, related to orthodenticle...
  47. Acampora D, Avantaggiato V, Tuorto F, Simeone A. Genetic control of brain morphogenesis through Otx gene dosage requirement. Development. 1997;124:3639-50 pubmed
    ..Previous data suggest that Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, might both contribute to brain ..
  48. Suda Y, Nakabayashi J, Matsuo I, Aizawa S. Functional equivalency between Otx2 and Otx1 in development of the rostral head. Development. 1999;126:743-57 pubmed
    Mice have two Otx genes, Otx1 and Otx2. Prior to gastrulation, Otx2 is expressed in the epiblast and visceral endoderm. As the primitive streak forms, Otx2 expression is restricted to the anterior parts of all three germ layers...
  49. Abraira V, Del Rio T, Tucker A, Slonimsky J, Keirnes H, Goodrich L. Cross-repressive interactions between Lrig3 and netrin 1 shape the architecture of the inner ear. Development. 2008;135:4091-9 pubmed publisher
    ..Thus, the Lrig3/Ntn1 feedback loop dictates when and where basement membrane breakdown occurs during canal development, revealing a new mechanism of complex tissue morphogenesis. ..
  50. Fossat N, Le Greneur C, Beby F, Vincent S, Godement P, Chatelain G, et al. A new GFP-tagged line reveals unexpected Otx2 protein localization in retinal photoreceptors. BMC Dev Biol. 2007;7:122 pubmed
    ..This opens up the way to live imaging of a highly dynamic actor of brain development and can be adapted to any mutant background to probe for genetic interaction between Otx2 and the mutated gene. ..
  51. Levantini E, Giorgetti A, Cerisoli F, Traggiai E, Guidi A, Martin R, et al. Unsuspected role of the brain morphogenetic gene Otx1 in hematopoiesis. Proc Natl Acad Sci U S A. 2003;100:10299-303 pubmed
    b>Otx1 belongs to the paired class of homeobox genes and plays a pivotal role in brain development. Here, we show that Otx1 is expressed in hematopoietic pluripotent and erythroid progenitor cells...
  52. Jones S, Johnson K, Yu H, Erway L, Alagramam K, Pollak N, et al. A quantitative survey of gravity receptor function in mutant mouse strains. J Assoc Res Otolaryngol. 2005;6:297-310 pubmed
    ..Interestingly, some heterozygote groups also showed abnormalities in one or more VsEP response parameters, suggesting that vestibular dysfunction, although less severe, may be present in some heterozygous animals. ..
  53. Simeone A, Puelles E, Acampora D. The Otx family. Curr Opin Genet Dev. 2002;12:409-15 pubmed
    b>Otx1 and Otx2, the murine homologs of the Drosophila orthodenticle gene, play a remarkable role in specification and regionalization of forebrain and midbrain...