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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Homeobox protein SIX3''' is a [[protein]] that in humans is encoded by the ''SIX3'' [[gene]].<ref name="pmid9889003">{{cite journal | vauthors = Granadino B, Gallardo ME, López-Ríos J, Sanz R, Ramos C, Ayuso C, Bovolenta P, Rodríguez de Córdoba S | title = Genomic cloning, structure, expression pattern, and chromosomal location of the human SIX3 gene | journal = Genomics | volume = 55 | issue = 1 | pages = 100–5 | date = Jan 1999 | pmid = 9889003 | pmc =  | doi = 10.1006/geno.1998.5611 }}</ref><ref name="pmid10369266">{{cite journal | vauthors = Wallis DE, Roessler E, Hehr U, Nanni L, Wiltshire T, Richieri-Costa A, Gillessen-Kaesbach G, Zackai EH, Rommens J, Muenke M | title = Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly | journal = Nature Genetics | volume = 22 | issue = 2 | pages = 196–8 | date = Jun 1999 | pmid = 10369266 | pmc =  | doi = 10.1038/9718 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SIX3 sine oculis homeobox homolog 3 (Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6496| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Sine oculis homeobox homolog 3 (Drosophila)
| HGNCid = 10889
| Symbol = SIX3
| AltSymbols =; HPE2
| OMIM = 603714
| ECnumber = 
| Homologene = 3947
| MGIid = 102764
| GeneAtlas_image1 = PBB_GE_SIX3_206634_at_tn.png
| Function = {{GNF_GO|id=GO:0003705 |text = RNA polymerase II transcription factor activity, enhancer binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0016564 |text = transcription repressor activity}} {{GNF_GO|id=GO:0043565 |text = sequence-specific DNA binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0001654 |text = eye development}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0007275 |text = multicellular organismal development}} {{GNF_GO|id=GO:0007420 |text = brain development}} {{GNF_GO|id=GO:0007601 |text = visual perception}} {{GNF_GO|id=GO:0016481 |text = negative regulation of transcription}} {{GNF_GO|id=GO:0030178 |text = negative regulation of Wnt receptor signaling pathway}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6496
    | Hs_Ensembl = ENSG00000138083
    | Hs_RefseqProtein = NP_005404
    | Hs_RefseqmRNA = NM_005413
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 2
    | Hs_GenLoc_start = 45022365
    | Hs_GenLoc_end = 45025945
    | Hs_Uniprot = O95343
    | Mm_EntrezGene = 20473
    | Mm_Ensembl = ENSMUSG00000038805
    | Mm_RefseqmRNA = XM_985177
    | Mm_RefseqProtein = XP_990271
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 17
    | Mm_GenLoc_start = 85529357
    | Mm_GenLoc_end = 85539117
    | Mm_Uniprot = Q4QQQ3
  }}
}}
'''Sine oculis homeobox homolog 3 (Drosophila)''', also known as '''SIX3''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: SIX3 sine oculis homeobox homolog 3 (Drosophila)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6496| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
The SIX homeobox 3 (SIX3) gene is crucial in [[Embryogenesis|embryonic development]] by providing necessary instructions for the formation of the [[forebrain]] and [[eye]] development. SIX3 is a [[transcription factor]] that binds to specific [[DNA]] sequences, controlling whether the gene is active or inactive. Activity of the SIX3 gene represses [[WNT1|Wnt1]] gene activity which ensures development of the forebrain and establishes the proper anterior posterior identity in the [[Brain|mammalian brain]]. By blocking Wnt1 activity, SIX3 is able to prevent abnormal expansion of the posterior portion of the brain into the anterior brain area.
{{PBB_Summary
| section_title =
| summary_text =
}}


==References==
During retinal development, SIX3 has been proven to hold a key responsibility in the activation of [[PAX6|Pax6]], the master regulator of [[eye development]]. Furthermore, SIX3 assumes its activity in the PLE (presumptive lens ectoderm), the region in which the [[Lens (anatomy)|lens]] is expected to develop. If its presence is removed from this region, the lens fails to thicken and construct itself to its proper morphological state. Also, SIX3 plays a strategic role in the activation of [[SOX2]].  
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Hecht BK, Hecht F, Münke M |title=Forebrain cleavage gene causing holoprosencephaly: deletion mapping to chromosome band 2p21. |journal=Am. J. Med. Genet. |volume=40 |issue= 1 |pages= 130 |year= 1991 |pmid= 1887845 |doi= 10.1002/ajmg.1320400131 }}
*{{cite journal  | author=Granadino B, Gallardo ME, López-Ríos J, ''et al.'' |title=Genomic cloning, structure, expression pattern, and chromosomal location of the human SIX3 gene. |journal=Genomics |volume=55 |issue= 1 |pages= 100-5 |year= 1999 |pmid= 9889003 |doi=  }}
*{{cite journal  | author=Wallis DE, Roessler E, Hehr U, ''et al.'' |title=Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly. |journal=Nat. Genet. |volume=22 |issue= 2 |pages= 196-8 |year= 1999 |pmid= 10369266 |doi= 10.1038/9718 }}
*{{cite journal  | author=Leppert GS, Yang JM, Sundin OH |title=Sequence and location of SIX3, a homeobox gene expressed in the human eye. |journal=Ophthalmic Genet. |volume=20 |issue= 1 |pages= 7-21 |year= 1999 |pmid= 10415461 |doi=  }}
*{{cite journal  | author=Ohto H, Kamada S, Tago K, ''et al.'' |title=Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya. |journal=Mol. Cell. Biol. |volume=19 |issue= 10 |pages= 6815-24 |year= 2000 |pmid= 10490620 |doi=  }}
*{{cite journal  | author=Mikkola I, Bruun JA, Holm T, Johansen T |title=Superactivation of Pax6-mediated transactivation from paired domain-binding sites by dna-independent recruitment of different homeodomain proteins. |journal=J. Biol. Chem. |volume=276 |issue= 6 |pages= 4109-18 |year= 2001 |pmid= 11069920 |doi= 10.1074/jbc.M008882200 }}
*{{cite journal  | author=Ohkura N, Ohkubo T, Maruyama K, ''et al.'' |title=The orphan nuclear receptor NOR-1 interacts with the homeobox containing protein Six3. |journal=Dev. Neurosci. |volume=23 |issue= 1 |pages= 17-24 |year= 2001 |pmid= 11173923 |doi=  }}
*{{cite journal  | author=Lengler J, Graw J |title=Regulation of the human SIX3 gene promoter. |journal=Biochem. Biophys. Res. Commun. |volume=287 |issue= 2 |pages= 372-6 |year= 2001 |pmid= 11554737 |doi= 10.1006/bbrc.2001.5605 }}
*{{cite journal  | author=Zhu CC, Dyer MA, Uchikawa M, ''et al.'' |title=Six3-mediated auto repression and eye development requires its interaction with members of the Groucho-related family of co-repressors. |journal=Development |volume=129 |issue= 12 |pages= 2835-49 |year= 2002 |pmid= 12050133 |doi=  }}
*{{cite journal  | author=López-Ríos J, Tessmar K, Loosli F, ''et al.'' |title=Six3 and Six6 activity is modulated by members of the groucho family. |journal=Development |volume=130 |issue= 1 |pages= 185-95 |year= 2003 |pmid= 12441302 |doi=  }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Laflamme C, Filion C, Bridge JA, ''et al.'' |title=The homeotic protein Six3 is a coactivator of the nuclear receptor NOR-1 and a corepressor of the fusion protein EWS/NOR-1 in human extraskeletal myxoid chondrosarcomas. |journal=Cancer Res. |volume=63 |issue= 2 |pages= 449-54 |year= 2003 |pmid= 12543801 |doi=  }}
*{{cite journal  | author=Del Bene F, Tessmar-Raible K, Wittbrodt J |title=Direct interaction of geminin and Six3 in eye development. |journal=Nature |volume=427 |issue= 6976 |pages= 745-9 |year= 2004 |pmid= 14973488 |doi= 10.1038/nature02292 }}
*{{cite journal  | author=Dubourg C, Lazaro L, Pasquier L, ''et al.'' |title=Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype-phenotype correlations. |journal=Hum. Mutat. |volume=24 |issue= 1 |pages= 43-51 |year= 2004 |pmid= 15221788 |doi= 10.1002/humu.20056 }}
*{{cite journal  | author=Laflamme C, Filion C, Labelle Y |title=Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1. |journal=Hum. Mutat. |volume=24 |issue= 6 |pages= 502-8 |year= 2005 |pmid= 15523651 |doi= 10.1002/humu.20102 }}
*{{cite journal  | author=Pasquier L, Dubourg C, Gonzales M, ''et al.'' |title=First occurrence of aprosencephaly/atelencephaly and holoprosencephaly in a family with a SIX3 gene mutation and phenotype/genotype correlation in our series of SIX3 mutations. |journal=J. Med. Genet. |volume=42 |issue= 1 |pages= e4 |year= 2006 |pmid= 15635066 |doi= 10.1136/jmg.2004.023416 }}
*{{cite journal  | author=Bendavid C, Dubourg C, Gicquel I, ''et al.'' |title=Molecular evaluation of foetuses with holoprosencephaly shows high incidence of microdeletions in the HPE genes. |journal=Hum. Genet. |volume=119 |issue= 1-2 |pages= 1-8 |year= 2007 |pmid= 16323008 |doi= 10.1007/s00439-005-0097-6 }}
*{{cite journal  | author=Manavathi B, Peng S, Rayala SK, ''et al.'' |title=Repression of Six3 by a corepressor regulates rhodopsin expression. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue= 32 |pages= 13128-33 |year= 2007 |pmid= 17666527 |doi= 10.1073/pnas.0705878104 }}
}}
{{refend}}


{{protein-stub}}
SIX3 has also been proven to play a role in repression of selected members of the Wnt family. In retinal development, SIX3 is responsible for the repression of [[WNT8B|Wnt8b]]. Also, in forebrain development, SIX3 is responsible for the repression of Wnt1 and activation of SHH, [[Sonic hedgehog (gene)|Sonic Hedgehog gene.]]
{{WikiDoc Sources}}
 
== Clinical significance ==
 
[[Mutation|Mutations]] in SIX3 are the cause of a severe brain malformation, called [[holoprosencephaly]] type 2 (HPE2). In HPE2, the brain fails to separate into two [[Brain hemispheres|hemispheres]] during early embryonic development, leading to eye and brain malformations, which result in serious facial abnormalities.<ref name="pmid10369266" />
 
A mutant [[zebrafish]] [[gene knockout|knockout]] model has been developed, in which the anterior part of the head was missing due to the atypical increase of Wnt1 activity. When injected with SIX3, these zebrafish embryos were able to successfully develop a normal forebrain.<ref name="pmid12569128">{{cite journal | vauthors = Lagutin OV, Zhu CC, Kobayashi D, Topczewski J, Shimamura K, Puelles L, Russell HR, McKinnon PJ, Solnica-Krezel L, Oliver G | title = Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development | journal = Genes & Development | volume = 17 | issue = 3 | pages = 368–79 | date = Feb 2003 | pmid = 12569128 | pmc = 195989 | doi = 10.1101/gad.1059403 }}</ref><ref name="pmid18094027">{{cite journal | vauthors = Lavado A, Lagutin OV, Oliver G | title = Six3 inactivation causes progressive caudalization and aberrant patterning of the mammalian diencephalon | journal = Development | volume = 135 | issue = 3 | pages = 441–50 | date = Feb 2008 | pmid = 18094027 | doi = 10.1242/dev.010082 }}</ref> When SIX3 was turned off in mice, resulting in a lack of retina formation due to excessive expression of Wnt8b in the region where the forebrain normally develops.<ref name="pmid20890044">{{cite journal | vauthors = Liu W, Lagutin O, Swindell E, Jamrich M, Oliver G | title = Neuroretina specification in mouse embryos requires Six3-mediated suppression of Wnt8b in the anterior neural plate | journal = The Journal of Clinical Investigation | volume = 120 | issue = 10 | pages = 3568–77 | date = Oct 2010 | pmid = 20890044 | pmc = 2947236 | doi = 10.1172/JCI43219 }}</ref> Both of these studies demonstrate the importance of SIX3 activity in brain and eye development.
 
== Interactions ==
 
SIX3 has been shown to [[Protein-protein interaction|interact]] with [[TLE1]]<ref name="pmid12441302">{{cite journal | vauthors = López-Ríos J, Tessmar K, Loosli F, Wittbrodt J, Bovolenta P | title = Six3 and Six6 activity is modulated by members of the groucho family | journal = Development | volume = 130 | issue = 1 | pages = 185–95 | date = Jan 2003 | pmid = 12441302 | doi = 10.1242/dev.00185 }}</ref> and [[Neuron-derived orphan receptor 1]].<ref name="pmid12543801">{{cite journal | vauthors = Laflamme C, Filion C, Bridge JA, Ladanyi M, Goldring MB, Labelle Y | title = The homeotic protein Six3 is a coactivator of the nuclear receptor NOR-1 and a corepressor of the fusion protein EWS/NOR-1 in human extraskeletal myxoid chondrosarcomas | journal = Cancer Research | volume = 63 | issue = 2 | pages = 449–54 | date = Jan 2003 | pmid = 12543801 | doi =  }}</ref><ref name="pmid11173923">{{cite journal | vauthors = Ohkura N, Ohkubo T, Maruyama K, Tsukada T, Yamaguchi K | title = The orphan nuclear receptor NOR-1 interacts with the homeobox containing protein Six3 | journal = Developmental Neuroscience | volume = 23 | issue = 1 | pages = 17–24 | year = 2001 | pmid = 11173923 | doi = 10.1159/000048692 }}</ref>
 
== References ==
{{Reflist}}
 
== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Hecht BK, Hecht F, Münke M | title = Forebrain cleavage gene causing holoprosencephaly: deletion mapping to chromosome band 2p21 | journal = American Journal of Medical Genetics | volume = 40 | issue = 1 | pages = 130 | date = Jul 1991 | pmid = 1887845 | doi = 10.1002/ajmg.1320400131 }}
* {{cite journal | vauthors = Leppert GS, Yang JM, Sundin OH | title = Sequence and location of SIX3, a homeobox gene expressed in the human eye | journal = Ophthalmic Genetics | volume = 20 | issue = 1 | pages = 7–21 | date = Mar 1999 | pmid = 10415461 | doi = 10.1076/opge.20.1.7.2298 }}
* {{cite journal | vauthors = Ohto H, Kamada S, Tago K, Tominaga SI, Ozaki H, Sato S, Kawakami K | title = Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya | journal = Molecular and Cellular Biology | volume = 19 | issue = 10 | pages = 6815–24 | date = Oct 1999 | pmid = 10490620 | pmc = 84678 | doi =  10.1128/mcb.19.10.6815}}
* {{cite journal | vauthors = Mikkola I, Bruun JA, Holm T, Johansen T | title = Superactivation of Pax6-mediated transactivation from paired domain-binding sites by dna-independent recruitment of different homeodomain proteins | journal = The Journal of Biological Chemistry | volume = 276 | issue = 6 | pages = 4109–18 | date = Feb 2001 | pmid = 11069920 | doi = 10.1074/jbc.M008882200 }}
* {{cite journal | vauthors = Ohkura N, Ohkubo T, Maruyama K, Tsukada T, Yamaguchi K | title = The orphan nuclear receptor NOR-1 interacts with the homeobox containing protein Six3 | journal = Developmental Neuroscience | volume = 23 | issue = 1 | pages = 17–24 | year = 2001 | pmid = 11173923 | doi = 10.1159/000048692 }}
* {{cite journal | vauthors = Lengler J, Graw J | title = Regulation of the human SIX3 gene promoter | journal = Biochemical and Biophysical Research Communications | volume = 287 | issue = 2 | pages = 372–6 | date = Sep 2001 | pmid = 11554737 | doi = 10.1006/bbrc.2001.5605 }}
* {{cite journal | vauthors = Zhu CC, Dyer MA, Uchikawa M, Kondoh H, Lagutin OV, Oliver G | title = Six3-mediated auto repression and eye development requires its interaction with members of the Groucho-related family of co-repressors | journal = Development | volume = 129 | issue = 12 | pages = 2835–49 | date = Jun 2002 | pmid = 12050133 | doi =  }}
* {{cite journal | vauthors = López-Ríos J, Tessmar K, Loosli F, Wittbrodt J, Bovolenta P | title = Six3 and Six6 activity is modulated by members of the groucho family | journal = Development | volume = 130 | issue = 1 | pages = 185–95 | date = Jan 2003 | pmid = 12441302 | doi = 10.1242/dev.00185 }}
* {{cite journal | vauthors = Laflamme C, Filion C, Bridge JA, Ladanyi M, Goldring MB, Labelle Y | title = The homeotic protein Six3 is a coactivator of the nuclear receptor NOR-1 and a corepressor of the fusion protein EWS/NOR-1 in human extraskeletal myxoid chondrosarcomas | journal = Cancer Research | volume = 63 | issue = 2 | pages = 449–54 | date = Jan 2003 | pmid = 12543801 | doi =  }}
* {{cite journal | vauthors = Del Bene F, Tessmar-Raible K, Wittbrodt J | title = Direct interaction of geminin and Six3 in eye development | journal = Nature | volume = 427 | issue = 6976 | pages = 745–9 | date = Feb 2004 | pmid = 14973488 | doi = 10.1038/nature02292 }}
* {{cite journal | vauthors = Dubourg C, Lazaro L, Pasquier L, Bendavid C, Blayau M, Le Duff F, Durou MR, Odent S, David V | title = Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype-phenotype correlations | journal = Human Mutation | volume = 24 | issue = 1 | pages = 43–51 | date = Jul 2004 | pmid = 15221788 | doi = 10.1002/humu.20056 }}
* {{cite journal | vauthors = Laflamme C, Filion C, Labelle Y | title = Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1 | journal = Human Mutation | volume = 24 | issue = 6 | pages = 502–8 | date = Dec 2004 | pmid = 15523651 | doi = 10.1002/humu.20102 }}
* {{cite journal | vauthors = Pasquier L, Dubourg C, Gonzales M, Lazaro L, David V, Odent S, Encha-Razavi F | title = First occurrence of aprosencephaly/atelencephaly and holoprosencephaly in a family with a SIX3 gene mutation and phenotype/genotype correlation in our series of SIX3 mutations | journal = Journal of Medical Genetics | volume = 42 | issue = 1 | pages = e4 | date = Jan 2005 | pmid = 15635066 | pmc = 1735902 | doi = 10.1136/jmg.2004.023416 }}
* {{cite journal | vauthors = Bendavid C, Dubourg C, Gicquel I, Pasquier L, Saugier-Veber P, Durou MR, Jaillard S, Frébourg T, Haddad BR, Henry C, Odent S, David V | title = Molecular evaluation of foetuses with holoprosencephaly shows high incidence of microdeletions in the HPE genes | journal = Human Genetics | volume = 119 | issue = 1-2 | pages = 1–8 | date = Mar 2006 | pmid = 16323008 | doi = 10.1007/s00439-005-0097-6 }}
* {{cite journal | vauthors = Manavathi B, Peng S, Rayala SK, Talukder AH, Wang MH, Wang RA, Balasenthil S, Agarwal N, Frishman LJ, Kumar R | title = Repression of Six3 by a corepressor regulates rhodopsin expression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 32 | pages = 13128–33 | date = Aug 2007 | pmid = 17666527 | pmc = 1941821 | doi = 10.1073/pnas.0705878104 }}
{{Refend}}
 
== External links ==
* [https://www.ncbi.nlm.nih.gov/books/NBK1378/  GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview]
 
{{Transcription factors|g3}}
 
[[Category:Transcription factors]]
[[Category:Developmental neuroscience]]

Latest revision as of 21:37, 19 February 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Homeobox protein SIX3 is a protein that in humans is encoded by the SIX3 gene.[1][2][3]

Function

The SIX homeobox 3 (SIX3) gene is crucial in embryonic development by providing necessary instructions for the formation of the forebrain and eye development. SIX3 is a transcription factor that binds to specific DNA sequences, controlling whether the gene is active or inactive. Activity of the SIX3 gene represses Wnt1 gene activity which ensures development of the forebrain and establishes the proper anterior posterior identity in the mammalian brain. By blocking Wnt1 activity, SIX3 is able to prevent abnormal expansion of the posterior portion of the brain into the anterior brain area.

During retinal development, SIX3 has been proven to hold a key responsibility in the activation of Pax6, the master regulator of eye development. Furthermore, SIX3 assumes its activity in the PLE (presumptive lens ectoderm), the region in which the lens is expected to develop. If its presence is removed from this region, the lens fails to thicken and construct itself to its proper morphological state. Also, SIX3 plays a strategic role in the activation of SOX2.

SIX3 has also been proven to play a role in repression of selected members of the Wnt family. In retinal development, SIX3 is responsible for the repression of Wnt8b. Also, in forebrain development, SIX3 is responsible for the repression of Wnt1 and activation of SHH, Sonic Hedgehog gene.

Clinical significance

Mutations in SIX3 are the cause of a severe brain malformation, called holoprosencephaly type 2 (HPE2). In HPE2, the brain fails to separate into two hemispheres during early embryonic development, leading to eye and brain malformations, which result in serious facial abnormalities.[2]

A mutant zebrafish knockout model has been developed, in which the anterior part of the head was missing due to the atypical increase of Wnt1 activity. When injected with SIX3, these zebrafish embryos were able to successfully develop a normal forebrain.[4][5] When SIX3 was turned off in mice, resulting in a lack of retina formation due to excessive expression of Wnt8b in the region where the forebrain normally develops.[6] Both of these studies demonstrate the importance of SIX3 activity in brain and eye development.

Interactions

SIX3 has been shown to interact with TLE1[7] and Neuron-derived orphan receptor 1.[8][9]

References

  1. ↑ Granadino B, Gallardo ME, López-Ríos J, Sanz R, Ramos C, Ayuso C, Bovolenta P, Rodríguez de Córdoba S (Jan 1999). "Genomic cloning, structure, expression pattern, and chromosomal location of the human SIX3 gene". Genomics. 55 (1): 100–5. doi:10.1006/geno.1998.5611. PMID 9889003.
  2. ↑ 2.0 2.1 Wallis DE, Roessler E, Hehr U, Nanni L, Wiltshire T, Richieri-Costa A, Gillessen-Kaesbach G, Zackai EH, Rommens J, Muenke M (Jun 1999). "Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly". Nature Genetics. 22 (2): 196–8. doi:10.1038/9718. PMID 10369266.
  3. ↑ "Entrez Gene: SIX3 sine oculis homeobox homolog 3 (Drosophila)".
  4. ↑ Lagutin OV, Zhu CC, Kobayashi D, Topczewski J, Shimamura K, Puelles L, Russell HR, McKinnon PJ, Solnica-Krezel L, Oliver G (Feb 2003). "Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development". Genes & Development. 17 (3): 368–79. doi:10.1101/gad.1059403. PMC 195989. PMID 12569128.
  5. ↑ Lavado A, Lagutin OV, Oliver G (Feb 2008). "Six3 inactivation causes progressive caudalization and aberrant patterning of the mammalian diencephalon". Development. 135 (3): 441–50. doi:10.1242/dev.010082. PMID 18094027.
  6. ↑ Liu W, Lagutin O, Swindell E, Jamrich M, Oliver G (Oct 2010). "Neuroretina specification in mouse embryos requires Six3-mediated suppression of Wnt8b in the anterior neural plate". The Journal of Clinical Investigation. 120 (10): 3568–77. doi:10.1172/JCI43219. PMC 2947236. PMID 20890044.
  7. ↑ López-Ríos J, Tessmar K, Loosli F, Wittbrodt J, Bovolenta P (Jan 2003). "Six3 and Six6 activity is modulated by members of the groucho family". Development. 130 (1): 185–95. doi:10.1242/dev.00185. PMID 12441302.
  8. ↑ Laflamme C, Filion C, Bridge JA, Ladanyi M, Goldring MB, Labelle Y (Jan 2003). "The homeotic protein Six3 is a coactivator of the nuclear receptor NOR-1 and a corepressor of the fusion protein EWS/NOR-1 in human extraskeletal myxoid chondrosarcomas". Cancer Research. 63 (2): 449–54. PMID 12543801.
  9. ↑ Ohkura N, Ohkubo T, Maruyama K, Tsukada T, Yamaguchi K (2001). "The orphan nuclear receptor NOR-1 interacts with the homeobox containing protein Six3". Developmental Neuroscience. 23 (1): 17–24. doi:10.1159/000048692. PMID 11173923.

Further reading

External links

Retrieved from "https://www.wikidoc.org/index.php?title=SIX3&oldid=1531687"