Six3

Summary

Gene Symbol: Six3
Description: sine oculis-related homeobox 3
Alias: E130112M24Rik, Six3a, Six3alpha, Six3b, Six3beta, homeobox protein SIX3, sine oculis homeobox homolog 3, sine oculis-related homeobox 3 homolog
Species: mouse
Products:     Six3

Top Publications

  1. Martinez Barbera J, Clements M, Thomas P, Rodriguez T, Meloy D, Kioussis D, et al. The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation. Development. 2000;127:2433-45 pubmed
    ..All together, these results demonstrate that Hex function is essential in definitive endoderm for normal development of the forebrain, liver and thyroid gland. ..
  2. Lagutin O, Zhu C, Furuta Y, Rowitch D, McMahon A, Oliver G. Six3 promotes the formation of ectopic optic vesicle-like structures in mouse embryos. Dev Dyn. 2001;221:342-9 pubmed
    ..Because of its early expression in the developing eye field, Six3 was initially thought to be the functional ortholog of the Drosophila so gene...
  3. Jin J, Gu S, McKinney P, Ding J. Expression and functional analysis of Tgif during mouse midline development. Dev Dyn. 2006;235:547-53 pubmed
    ..One interpretation of these results is that the loss of TGIF function is compensated by other TGF-beta antagonists such as c-Ski and SnoN during vertebrate anterior neural development. ..
  4. Mukhopadhyay M, Shtrom S, Rodriguez Esteban C, Chen L, Tsukui T, Gomer L, et al. Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. Dev Cell. 2001;1:423-34 pubmed
  5. Dattani M, Martinez Barbera J, Thomas P, Brickman J, Gupta R, Mårtensson I, et al. Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat Genet. 1998;19:125-33 pubmed
    ..These data suggest an important role for Hesx1/HESX1 in forebrain, midline and pituitary development in mouse and human. ..
  6. Satoh K, Kasai M, Ishidao T, Tago K, Ohwada S, Hasegawa Y, et al. Anteriorization of neural fate by inhibitor of beta-catenin and T cell factor (ICAT), a negative regulator of Wnt signaling. Proc Natl Acad Sci U S A. 2004;101:8017-21 pubmed
    ..These results suggest that ICAT plays an important role in the anteriorization of neural cells by inhibiting the posteriorizing activity of Wnt signaling. ..
  7. Yamada R, Mizutani Koseki Y, Hasegawa T, Osumi N, Koseki H, Takahashi N. Cell-autonomous involvement of Mab21l1 is essential for lens placode development. Development. 2003;130:1759-70 pubmed
    ..with delayed and insufficient expression of Foxe3, which is also required for lens development, while Maf, Sox2, Six3 and PAX6 levels are not significantly affected...
  8. Jeong Y, Leskow F, El Jaick K, Roessler E, Muenke M, Yocum A, et al. Regulation of a remote Shh forebrain enhancer by the Six3 homeoprotein. Nat Genet. 2008;40:1348-53 pubmed publisher
    ..a DNA affinity-capture assay, we screened the SBE2 sequence for DNA-binding proteins and identified members of the Six3 and Six6 homeodomain family as candidate regulators of Shh transcription...
  9. Grimm C, Chatterjee B, Favor J, Immervoll T, Loster J, Klopp N, et al. Aphakia (ak), a mouse mutation affecting early eye development: fine mapping, consideration of candidate genes and altered Pax6 and Six3 gene expression pattern. Dev Genet. 1998;23:299-316 pubmed
    ..In the lens remnants, Pax6 and Six3 are expressed, whereas in the persisting lens stalk only Pax6 was detected...

More Information

Publications62

  1. 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. ..
  2. Ashery Padan R, Marquardt T, Zhou X, Gruss P. Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye. Genes Dev. 2000;14:2701-11 pubmed
  3. Morcillo J, Martinez Morales J, Trousse F, Fermin Y, Sowden J, Bovolenta P. Proper patterning of the optic fissure requires the sequential activity of BMP7 and SHH. Development. 2006;133:3179-90 pubmed
    ..Collectively, these data indicate that BMP7 is required for retinal fissure formation and that its activity is needed, before SHH signalling, for the generation of PAX2-positive cells at the optic disc. ..
  4. Zhu C, Dyer M, Uchikawa M, Kondoh H, Lagutin O, Oliver G. Six3-mediated auto repression and eye development requires its interaction with members of the Groucho-related family of co-repressors. Development. 2002;129:2835-49 pubmed
    Recent findings suggest that Six3, a member of the evolutionarily conserved So/Six homeodomain family, plays an important role in vertebrate visual system development...
  5. Geng X, Lavado A, Lagutin O, Liu W, Oliver G. Expression of Six3 Opposite Strand (Six3OS) during mouse embryonic development. Gene Expr Patterns. 2007;7:252-7 pubmed
    ..High levels of noncoding transcripts of the Six3 Opposite Strand (Six3OS) were recently identified in the embryonic and postnatal retina of the mouse...
  6. Alfano G, Vitiello C, Caccioppoli C, Caramico T, Carola A, Szego M, et al. Natural antisense transcripts associated with genes involved in eye development. Hum Mol Genet. 2005;14:913-23 pubmed
    ..We describe the identification of eight novel mouse NATs associated with transcription factors (Pax6, Pax2, Six3, Six6, Otx2, Crx, Rax and Vax2) that play an important role in eye development and function...
  7. Acampora D, Boyl P, Signore M, Martinez Barbera J, Ilengo C, Puelles E, et al. OTD/OTX2 functional equivalence depends on 5' and 3' UTR-mediated control of Otx2 mRNA for nucleo-cytoplasmic export and epiblast-restricted translation. Development. 2001;128:4801-13 pubmed
    ..These data provide novel in vivo evidence supporting the concept that during evolution pre-existing gene functions have been recruited into new developmental pathways by modifying their regulatory control. ..
  8. Storm E, Garel S, Borello U, Hebert J, Martinez S, McConnell S, et al. Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers. Development. 2006;133:1831-44 pubmed
    ..These data suggest that Fgf8 functions to coordinate multiple patterning centers, and that modifications in the relative strength of FGF signaling can have profound effects on the relative size and nature of telencephalic subdivisions. ..
  9. Liu W, Lagutin O, Mende M, Streit A, Oliver G. Six3 activation of Pax6 expression is essential for mammalian lens induction and specification. EMBO J. 2006;25:5383-95 pubmed
    The homeobox gene Six3 regulates forebrain development. Here we show that Six3 is also crucial for lens formation. Conditional deletion of mouse Six3 in the presumptive lens ectoderm (PLE) disrupted lens formation...
  10. Nguyen M, Arnheiter H. Signaling and transcriptional regulation in early mammalian eye development: a link between FGF and MITF. Development. 2000;127:3581-91 pubmed
  11. Abe Y, Oka A, Mizuguchi M, Igarashi T, Ishikawa S, Aburatani H, et al. EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functionally. Hum Mutat. 2009;30:E946-55 pubmed publisher
    ..EYA4 was co-immunoprecipitated with SIX3, the product of one of the known HPE genes...
  12. Furuta Y, Lagutin O, Hogan B, Oliver G. Retina- and ventral forebrain-specific Cre recombinase activity in transgenic mice. Genesis. 2000;26:130-2 pubmed
  13. Aoto K, Shikata Y, Imai H, Matsumaru D, Tokunaga T, Shioda S, et al. Mouse Shh is required for prechordal plate maintenance during brain and craniofacial morphogenesis. Dev Biol. 2009;327:106-20 pubmed publisher
    ..These findings provide new insight into the mechanism underlying HPE pathoetiology during dynamic brain and craniofacial morphogenesis. ..
  14. Lagutin O, Zhu C, Kobayashi D, Topczewski J, Shimamura K, Puelles L, et al. Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development. Genes Dev. 2003;17:368-79 pubmed
    ..In Six3(-/-) mice, the prosencephalon was severely truncated, and the expression of Wnt1 was rostrally expanded, a finding ..
  15. Lewis S, Khoo P, Andrea De Young R, Bildsoe H, Wakamiya M, Behringer R, et al. Genetic interaction of Gsc and Dkk1 in head morphogenesis of the mouse. Mech Dev. 2007;124:157-165 pubmed
    ..Our results show that Gsc and Dkk1 functions are non-redundant in the anterior mesendoderm for normal anterior development and Gsc may influence Wnt signalling as a negative regulator. ..
  16. Warr N, Powles Glover N, Chappell A, Robson J, Norris D, Arkell R. Zic2-associated holoprosencephaly is caused by a transient defect in the organizer region during gastrulation. Hum Mol Genet. 2008;17:2986-96 pubmed publisher
    ..The analysis provides genetic evidence that Zic2 functions during organizer formation and that the PCP develops via a multi-step process. ..
  17. Tétreault N, Champagne M, Bernier G. The LIM homeobox transcription factor Lhx2 is required to specify the retina field and synergistically cooperates with Pax6 for Six6 trans-activation. Dev Biol. 2009;327:541-50 pubmed publisher
    ..demarcates the presumptive retina field at the neural plate stage and Lhx2 inactivation delays initiation of Rx, Six3 and Pax6 expression in this domain...
  18. Kimura C, Yoshinaga K, Tian E, Suzuki M, Aizawa S, Matsuo I. Visceral endoderm mediates forebrain development by suppressing posteriorizing signals. Dev Biol. 2000;225:304-21 pubmed
    ..These results suggest that distal visceral endoderm cells move to the future anterior side to generate a prospective forebrain territory indirectly, by preventing posteriorizing signals. ..
  19. 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
    ..Moreover, our data lead us to hypothesize that the differential post-transcriptional control existing between VE and epiblast cells may potentially contribute to fundamental regulatory mechanisms required for head specification. ..
  20. Oliver G, Mailhos A, Wehr R, Copeland N, Jenkins N, Gruss P. Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development. 1995;121:4045-55 pubmed
    ..In this paper, we report the isolation of a sequence-related gene referred to as Six3. Based on its amino acid sequence, this gene can be included in the new Six/sine oculis subclass of homeobox genes...
  21. Martinez Barbera J, Rodriguez T, Beddington R. The homeobox gene Hesx1 is required in the anterior neural ectoderm for normal forebrain formation. Dev Biol. 2000;223:422-30 pubmed
    ..5- and 7.5-dpc Hesx1(-/-) mutants. Expression of the ANE markers Six3 and Rax/Rx was also unperturbed in the Hesx1(-/-) mutants from late gastrula to late headfold stages...
  22. Manuel M, Pratt T, Liu M, Jeffery G, Price D. Overexpression of Pax6 results in microphthalmia, retinal dysplasia and defective retinal ganglion cell axon guidance. BMC Dev Biol. 2008;8:59 pubmed publisher
    ..Here, we examined the consequences of over-expression for the eye and its axonal connections...
  23. Furuta Y, Hogan B. BMP4 is essential for lens induction in the mouse embryo. Genes Dev. 1998;12:3764-75 pubmed
    ..Based on these results we propose that BMP4 is required for the optic vesicle to manifest its lens-inducing activity, by regulating downstream genes and/or serving as one component of multiple inductive signals. ..
  24. Andersson O, Reissmann E, Jörnvall H, Ibanez C. Synergistic interaction between Gdf1 and Nodal during anterior axis development. Dev Biol. 2006;293:370-81 pubmed
    ..These results indicate that GDF-1 and Nodal converge on ALK4 in the anterior primitive streak to control the formation of organizing centers that are necessary for normal forebrain and branchial arch development. ..
  25. Purcell P, Oliver G, Mardon G, Donner A, Maas R. Pax6-dependence of Six3, Eya1 and Dach1 expression during lens and nasal placode induction. Gene Expr Patterns. 2005;6:110-8 pubmed
    ..sine oculis (so) belongs to the so/Six gene family, and Six3 is prominently expressed in the developing mammalian eye...
  26. Oliver G, Wehr R, Jenkins N, Copeland N, Cheyette B, Hartenstein V, et al. Homeobox genes and connective tissue patterning. Development. 1995;121:693-705 pubmed
    ..Six 1 and Six 2 also are expressed in skeletal and smooth muscle, respectively. These genes may participate in the patterning of the distal tendons of the limb phalanges by setting positional values along the limb axes. ..
  27. Goudreau G, Petrou P, Reneker L, Graw J, Löster J, Gruss P. Mutually regulated expression of Pax6 and Six3 and its implications for the Pax6 haploinsufficient lens phenotype. Proc Natl Acad Sci U S A. 2002;99:8719-24 pubmed
    ..We found that Six3 expression was specifically reduced in lenses of Pax6 heterozygous mouse embryos...
  28. Boyl P, Signore M, Acampora D, Martinez Barbera J, Ilengo C, Annino A, et al. Forebrain and midbrain development requires epiblast-restricted Otx2 translational control mediated by its 3' UTR. Development. 2001;128:2989-3000 pubmed
    ..This leads us to hypothesise that this control might have important evolutionary implications. ..
  29. Yang Y, Klingensmith J. Roles of organizer factors and BMP antagonism in mammalian forebrain establishment. Dev Biol. 2006;296:458-75 pubmed
    ..These results lead to a model in which BMP antagonism supplied by exogenous tissues promotes forebrain establishment and maintenance in the murine ectoderm. ..
  30. Hoodless P, Pye M, Chazaud C, Labbe E, Attisano L, Rossant J, et al. FoxH1 (Fast) functions to specify the anterior primitive streak in the mouse. Genes Dev. 2001;15:1257-71 pubmed
    ..These results show that FoxH1 functions in an activin/nodal-Smad signaling pathway that acts upstream of Foxa2 and is required specifically for patterning the APS and node in the mouse. ..
  31. Rhinn M, Dierich A, Shawlot W, Behringer R, Le Meur M, Ang S. Sequential roles for Otx2 in visceral endoderm and neuroectoderm for forebrain and midbrain induction and specification. Development. 1998;125:845-56 pubmed
    ..However, in the absence of Otx2, expression of important regulatory genes, such as Hesx1/Rpx, Six3, Pax2, Wnt1 and En, fail to be initiated or maintained in the neural plate...
  32. Hirata T, Nakazawa M, Muraoka O, Nakayama R, Suda Y, Hibi M. Zinc-finger genes Fez and Fez-like function in the establishment of diencephalon subdivisions. Development. 2006;133:3993-4004 pubmed
    ..These data indicate that Fez and Fezl repress the caudal diencephalon fate in the rostral diencephalon, and ZLI formation probably depends on Fez/Fezl-mediated formation of diencephalon subdivisions. ..
  33. Zhao H, Yang Y, Partanen J, Ciruna B, Rossant J, Robinson M. Fibroblast growth factor receptor 1 (Fgfr1) is not essential for lens fiber differentiation in mice. Mol Vis. 2006;12:15-25 pubmed
    ..Overall, our results demonstrate that Fgfr1 is not cell autonomously essential for lens development and suggests functional redundancy among different FGF receptor genes with respect to lens fiber differentiation. ..
  34. Mao J, McKean D, Warrier S, Corbin J, Niswander L, Zohn I. The iron exporter ferroportin 1 is essential for development of the mouse embryo, forebrain patterning and neural tube closure. Development. 2010;137:3079-88 pubmed publisher
    ..Finally, we demonstrate that this loss of forebrain maintenance is due in part to the iron deficiency that results from the absence of fully functional Fpn1. ..
  35. Cammas L, Trensz F, Jellali A, Ghyselinck N, Roux M, Dolle P. Retinoic acid receptor (RAR)-alpha is not critically required for mediating retinoic acid effects in the developing mouse retina. Invest Ophthalmol Vis Sci. 2010;51:3281-90 pubmed publisher
    ..These data suggest that retinoic acid regulates neural retinal development through other, possibly RAR-independent, pathways. ..
  36. Cheng X, Hsu C, Currle D, Hu J, Barkovich A, Monuki E. Central roles of the roof plate in telencephalic development and holoprosencephaly. J Neurosci. 2006;26:7640-9 pubmed
    ..These findings establish selective roles for roof plate-dependent Bmp signaling in dorsal telencephalic patterning and HPE and define novel candidate genes for the human disorder. ..
  37. Pyrgaki C, Liu A, Niswander L. Grainyhead-like 2 regulates neural tube closure and adhesion molecule expression during neural fold fusion. Dev Biol. 2011;353:38-49 pubmed publisher
    ..Taken together, our studies point to a complex regulation of neural tube fusion and highlight the importance of comparisons between these two models to understand more fully the molecular pathways of embryonic tissue closure. ..
  38. Compagnucci C, Fish J, Schwark M, Tarabykin V, Depew M. Pax6 regulates craniofacial form through its control of an essential cephalic ectodermal patterning center. Genesis. 2011;49:307-25 pubmed publisher
    ..Pax6 therefore regulates craniofacial form, at stages when CNC has just arrived in the frontonasal region, through its control of surface cephalic ectodermal competence to form an essential craniofacial patterning center. ..
  39. Li J, Joyner A. Otx2 and Gbx2 are required for refinement and not induction of mid-hindbrain gene expression. Development. 2001;128:4979-91 pubmed
    ..Furthermore, Otx2 and Gbx2 are required to suppress hindbrain and midbrain development, respectively, and thus allow establishment of the normal spatial domains of Fgf8 and other genes. ..
  40. Carbe C, Zhang X. Lens induction requires attenuation of ERK signaling by Nf1. Hum Mol Genet. 2011;20:1315-23 pubmed publisher
    ..As a member of NCFC family genes, Nf1 represents the first example that attenuation of Ras-MAPK kinase signaling pathway is essential for normal lens development...
  41. Iratni R, Yan Y, Chen C, Ding J, Zhang Y, Price S, et al. Inhibition of excess nodal signaling during mouse gastrulation by the transcriptional corepressor DRAP1. Science. 2002;298:1996-9 pubmed
    ..We propose that DRAP1 limits the spread of a morphogenetic signal by down-modulating the response to the Nodal autoregulatory loop. ..
  42. Lee B, Song H, Rizzoti K, Son Y, Yoon J, Baek K, et al. Genomic code for Sox2 binding uncovers its regulatory role in Six3 activation in the forebrain. Dev Biol. 2013;381:491-501 pubmed publisher
    ..b>Six3, a homeobox gene associated with holoprosencephaly, a forebrain midline defect, was identified as a Sox2 ..
  43. Conte I, Morcillo J, Bovolenta P. Comparative analysis of Six 3 and Six 6 distribution in the developing and adult mouse brain. Dev Dyn. 2005;234:718-25 pubmed
    ..These distinct patterns support the idea that Six 3 and Six 6 are differentially required during forebrain development. ..
  44. Medina Martinez O, Shah R, Jamrich M. Pitx3 controls multiple aspects of lens development. Dev Dyn. 2009;238:2193-201 pubmed publisher
    ..In general, our study shows that the abnormal phenotype of the ak lenses is not due to just one molecular pathway, rather in the absence of Pitx3 expression multiple aspects of lens development are disrupted. ..
  45. Ferran J, Sánchez Arrones L, Bardet S, Sandoval J, Martinez de la Torre M, Puelles L. Early pretectal gene expression pattern shows a conserved anteroposterior tripartition in mouse and chicken. Brain Res Bull. 2008;75:295-8 pubmed publisher
    ..We explore here Pax3, Pax6 and Six3 mRNA expression (and PAX3 immunoreactivity) in both chicken and mice, with the aim to compare their respective ..
  46. Anselme I, Laclef C, Lanaud M, Ruther U, Schneider Maunoury S. Defects in brain patterning and head morphogenesis in the mouse mutant Fused toes. Dev Biol. 2007;304:208-20 pubmed
    ..Given the diversity, localisation and nature of the defects, we propose that some of them are caused by the elimination of the IrxB cluster, while others result from the loss of one or several of the Fts, Ftm and Fto genes. ..
  47. de Melo J, Du G, Fonseca M, Gillespie L, Turk W, Rubenstein J, et al. Dlx1 and Dlx2 function is necessary for terminal differentiation and survival of late-born retinal ganglion cells in the developing mouse retina. Development. 2005;132:311-22 pubmed
    ..Herein, we propose a model whereby early-born RGCs are Dlx1 and Dlx2 independent, but Dlx function is necessary for terminal differentiation of late-born RGC progenitors. ..
  48. Yamamoto M, Meno C, Sakai Y, Shiratori H, Mochida K, Ikawa Y, et al. The transcription factor FoxH1 (FAST) mediates Nodal signaling during anterior-posterior patterning and node formation in the mouse. Genes Dev. 2001;15:1242-56 pubmed
    ..These results indicate that a Nodal-FoxH1 signaling pathway plays a central role in A-P patterning and node formation in the mouse. ..
  49. Zhang L, Mathers P, Jamrich M. Function of Rx, but not Pax6, is essential for the formation of retinal progenitor cells in mice. Genesis. 2000;28:135-42 pubmed
    ..In this study, we have investigated the expression of Otx2, Six3, and Pax6 in Rx deficient embryos...
  50. Takata N, Sakakura E, Sasai Y. IGF-2/IGF-1R signaling has distinct effects on Sox1, Irx3, and Six3 expressions during ES cell derived-neuroectoderm development in vitro. In Vitro Cell Dev Biol Anim. 2016;52:607-15 pubmed publisher
    ..In contrast, the anterior neural marker Six3 was downregulated by IGF-2/IGF-1R signaling...
  51. Di Gregorio A, Sancho M, Stuckey D, Crompton L, Godwin J, Mishina Y, et al. BMP signalling inhibits premature neural differentiation in the mouse embryo. Development. 2007;134:3359-69 pubmed
    ..Together, our results demonstrate that inhibition of BMP signalling has a central role during neural induction in mammals and suggest that FGFs do not act as neural inducers in the post-implantation mouse embryo. ..
  52. Leung A, Wong S, Chan D, Tam P, Cheah K. Loss of procollagen IIA from the anterior mesendoderm disrupts the development of mouse embryonic forebrain. Dev Dyn. 2010;239:2319-29 pubmed publisher
    ..Genetic interaction studies reveal that IIA function in forebrain and face development does not involve bone morphogenetic protein receptor 1A (BMPR1A)- or NODAL-mediated signaling activity. ..
  53. Bibb L, Holt J, Tarttelin E, Hodges M, Gregory Evans K, Rutherford A, et al. Temporal and spatial expression patterns of the CRX transcription factor and its downstream targets. Critical differences during human and mouse eye development. Hum Mol Genet. 2001;10:1571-9 pubmed
    ..These data support concerns about the extent to which we can extrapolate from rodent models regarding embryonic development and disease pathophysiology. ..