SIX3 Bos taurus
SIX3 Canis lupus familiaris
six3a Danio rerio
SIX3 Gallus gallus
SIX3 Homo sapiens
SIX3 Pan troglodytes
Six3 Rattus norvegicus
six3 Xenopus (Silurana) tropicalis
Disease relevance of Six3
High impact information on Six3
Biological context of Six3
Anatomical context of Six3
Associations of Six3 with chemical compounds
Regulatory relationships of Six3
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Analytical, diagnostic and therapeutic context of Six3
Six3 - sine oculis-related homeobox 3
Mus musculus
Synonyms: E130112M24Rik, Homeobox protein SIX3, Sine oculis homeobox homolog 3, Six3a, Six3alpha, ...
Zhu, C.C. et al., Graw, J. et al., Lagutin, O.V. et al., Oliver, G. et al., Jean, D. et al., et al.
Meyer, Selby, Löster, Graw, Puk, Placzek, Favor, Münster, Hrabé de Angelis, Haubst, Pretsch, Nürnberg, Dyer, Soewarto, Kimura, Ohyama, Wolf, Fuchs, Ellis,
Aphakia (ak), a mouse mutation affecting early eye development: fine mapping, consideration of candidate genes and altered Pax6 and Six3 gene expression pattern [1].
Finally, based on the chromosomal localization and the expression pattern of the mouse Six3 gene, the human Six3 cognate could be a good candidate to be at least one of the genes affected in patients with holoprosencephaly type 2 due to an interstitial deletion of 2p21-p22 [2].
Ectopic expression of Six3 in chick and fish embryos, together with the use of in vivo and in vitro DNA-binding assays, allowed us to determine that Six3 is a direct negative regulator of Wnt1 expression [3].
A vertebrate member of the so/Six gene family, Six3, is expressed in the developing eye and forebrain [4].
Injection of Six3 RNA into medaka fish embryos causes ectopic Pax6 and Rx2 expression in midbrain and cerebellum, resulting in the formation of ectopic retinal primordia [4].
Furthermore, expression of Pax6 and Six3, molecular markers for lens induction, were decreased in the Frs2alpha(2F/2F) presumptive lens ectoderm [5].
Accordingly, we show a rescue of the Pax6 haploinsufficient lens phenotype after lens-specific expression of Six3 in transgenic mice [6].
Reporter gene analysis used Crygf and Six3 promoter fragments in front of a luciferase gene and HEK293 cells as recipients [7].
This result is supported by the functional analysis of corresponding expression constructs in cell culture, where the Aey11 and Aey18 alleles did not show a stimulation of the Six3 promotor or an inhibition of the Crygf promoter (as wild-type constructs do) [7].
Six6 (Optx2) is a novel murine Six3-related homeobox gene that demarcates the presumptive pituitary/hypothalamic axis and the ventral optic stalk [8].
Absence of elevated apoptotic activity, but reduced cell proliferation together with the ectopic activation of Six3 expression in the presumptive PVN, indicates a critical role for Otp in terminal differentiation and maturation of these neuroendocrine cell lineages [9].
This region shares a homology with the distal region of mouse chromosome 17 where Six3 has been mapped [2].
Six3 expression in the pre-placode lens ectoderm is initially Pax6-independent, but subsequently both its expression and nuclear localization become Pax6-dependent [10].
The specificity of the interaction was validated by co-immunoprecipitation of Six3 and Grg4 complexes from cell lines [11].
Overexpression of wild type Six3 by in vivo retroviral infection of newborn rat retinae led to an altered photoreceptor phenotype, while the in ovo electroporation of chicken embryos resulted in failure of lens placode invagination and production of delta-crystallin-negative cells within the placode [11].
Here, we demonstrate that Shh and Bmp7 from the adjacent prechordal mesoderm govern hypothalamic neural fate, their sequential action controlling hypothalamic dopaminergic neuron generation in a Six3-dependent manner [12].
Expression of Six3 subfamily genes (Six3.1, Six3.2, Six6.1, and Six6.2) was restricted to the developing head, where expression was especially observed in derivatives of the forebrain (eyes, optic stalks, the hypothalamus and pituitary gland) [13].
Pax6 is expressed in lens progenitor cells before the onset of crystallin expression and it serves as an important regulatory factor required for expression of c-Maf, MafA/L-Maf, Six3, Prox1 and retinoic acid signaling both in lens precursor cells and the developing lens [14].
Using ChIP, electrophoretic mobility shift assay, and luciferase reporter assays, we determined that Six3 activates Pax6 and Sox2 expression [15].
When compared to Six6, Six3 expression pattern was highly similar, but with a generally broader transcripts distribution in the brain and in the visual system [8].
In Six3(-/-) mice, the prosencephalon was severely truncated, and the expression of Wnt1 was rostrally expanded, a finding that indicates that the mutant head was posteriorized [3].
Loss of optic vesicle RA signaling does not effect expression of early determinants of retina at the optic vesicle stage (Pax6, Six3, Rx, Mitf) [16].
We also investigated the proper patterning of structures adjacent to the prechordal plate by performing in situ hybridization of HNF-3beta, Six-3 and BF-1, genes whose expression domains remained unchanged [17].
Regulation of proliferation, cell fate specification and differentiation by the homeodomain proteins Prox1, Six3, and Chx10 in the developing retina [18].
Using PCR, we identified a specific DNA motif that is bound by Six3 and we demonstrated that Six3 acts as a potent transcriptional repressor upon its interaction with Groucho-related members [11].
Aphakia (ak), a mouse mutation affecting early eye development: fine mapping, consideration of candidate genes and altered Pax6 and Six3 gene expression pattern. Grimm, C., Chatterjee, B., Favor, J., Immervoll, T., Löster, J., Klopp, N., Sandulache, R., Graw, J. Dev. Genet. (1998) [Pubmed]
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. Oliver, G., Mailhos, A., Wehr, R., Copeland, N.G., Jenkins, N.A., Gruss, P. Development (1995) [Pubmed]
Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development. Lagutin, O.V., Zhu, C.C., Kobayashi, D., Topczewski, J., Shimamura, K., Puelles, L., Russell, H.R., McKinnon, P.J., Solnica-Krezel, L., Oliver, G. Genes Dev. (2003) [Pubmed]
Six3 overexpression initiates the formation of ectopic retina. Loosli, F., Winkler, S., Wittbrodt, J. Genes Dev. (1999) [Pubmed]
Tyrosine phosphorylation sites on FRS2alpha responsible for Shp2 recruitment are critical for induction of lens and retina. Gotoh, N., Ito, M., Yamamoto, S., Yoshino, I., Song, N., Wang, Y., Lax, I., Schlessinger, J., Shibuya, M., Lang, R.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
Mutually regulated expression of Pax6 and Six3 and its implications for the Pax6 haploinsufficient lens phenotype. Goudreau, G., Petrou, P., Reneker, L.W., Graw, J., Löster, J., Gruss, P. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
Three novel Pax6 alleles in the mouse leading to the same small-eye phenotype caused by different consequences at target promoters. Graw, J., Löster, J., Puk, O., Münster, D., Haubst, N., Soewarto, D., Fuchs, H., Meyer, B., Nürnberg, P., Pretsch, W., Selby, P., Favor, J., Wolf, E., Hrabé de Angelis, M. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
Six6 (Optx2) is a novel murine Six3-related homeobox gene that demarcates the presumptive pituitary/hypothalamic axis and the ventral optic stalk. Jean, D., Bernier, G., Gruss, P. Mech. Dev. (1999) [Pubmed]
The murine Otp homeobox gene plays an essential role in the specification of neuronal cell lineages in the developing hypothalamus. Wang, W., Lufkin, T. Dev. Biol. (2000) [Pubmed]
Pax6-dependence of Six3, Eya1 and Dach1 expression during lens and nasal placode induction. Purcell, P., Oliver, G., Mardon, G., Donner, A.L., Maas, R.L. Gene Expr. Patterns (2005) [Pubmed]
Six3-mediated auto repression and eye development requires its interaction with members of the Groucho-related family of co-repressors. Zhu, C.C., Dyer, M.A., Uchikawa, M., Kondoh, H., Lagutin, O.V., Oliver, G. Development (2002) [Pubmed]
Directed differentiation of neural cells to hypothalamic dopaminergic neurons. Ohyama, K., Ellis, P., Kimura, S., Placzek, M. Development (2005) [Pubmed]
Molecular cloning and embryonic expression of Xenopus Six homeobox genes. Ghanbari, H., Seo, H.C., Fjose, A., Brändli, A.W. Mech. Dev. (2001) [Pubmed]
Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens. Cvekl, A., Yang, Y., Chauhan, B.K., Cveklova, K. Int. J. Dev. Biol. (2004) [Pubmed]
Six3 activation of Pax6 expression is essential for mammalian lens induction and specification. Liu, W., Lagutin, O.V., Mende, M., Streit, A., Oliver, G. EMBO J. (2006) [Pubmed]
Raldh2 expression in optic vesicle generates a retinoic acid signal needed for invagination of retina during optic cup formation. Mic, F.A., Molotkov, A., Molotkova, N., Duester, G. Dev. Dyn. (2004) [Pubmed]
Goosecoid and cerberus-like do not interact during mouse embryogenesis. Borges, A.C., Marques, S., Belo, J.A. Int. J. Dev. Biol. (2002) [Pubmed]
Regulation of proliferation, cell fate specification and differentiation by the homeodomain proteins Prox1, Six3, and Chx10 in the developing retina. Dyer, M.A. Cell Cycle (2003) [Pubmed]