Source: http://atlasgeneticsoncology.org/Genes/GC_PAX6.html
Timestamp: 2019-04-24 03:07:21+00:00

Document:
Description The PAX6 coding region extends over a genomic interval of 16-17 kb and comprise 10 (isoform a) and 11 exons (isoform b).
Transcription Three transcripts have been identified, originating from alternative promoter usage (variant 3) or alternative splicing (variant 2, additional in-frame coding 42 bp exon downstream of exon 5 of variant 1); transcription is from centromere to telomere.
There are two isoforms of PAX6, PAX6a and PAX6b with additional 14 extra amino acids in the paired box DNA binding domain. PAX6a, 423 amino acids, ~47 kDa; PAX6b, 436 amino acids, ~49 kDa.
Description PAX6 belongs to the paired box family of transcription factors, contains two DNA binding domains, a paired box (PD) and a paired-type homeodomain (HD), and a carboxyl-terminal transactivation domain rich of proline, serine, and threonine (PST).
Expression PAX6, predominately in form of PAX6a, is expressed in the developing sensory organs (including eye, nasal and olfactory tissues), central nervous system (including forebrain, hindbrain, and spinal cord), and endocrine system (including anterior pituitary gland and pancreas) in human and rodent (Walther and Gruss., 1991; Stoykova and Gruss., 1994; Davis and Reed., 1996; Terzic and Saraga-Babic., 1999; Pinson et al., 2005). PAX6 expression is sustained into adulthood in certain areas of the brain, including, hippocampal dentate gyrus (Maekawa et al., 2005; Nacher et al., 2005), ependymal layer and the subventricular zone of the lateral ventricle (Hack et al., 2005; Kohwi et al., 2005), radial glia-like cells (Gubert et al., 2009), and in mature endocrine cells in pancreas (St-Onge et al., 1997). PAX6 transcription is regulated by two promoters, P0 and P1, which are remarkably conserved in evolution in both of their nucleotide sequence arrangement and functional control of special and temporal expression of PAX6 in development (Xu and Saunders, 1997; Okladnova et al., 1998a; Williams et al., 1998; Xu and Saunders, 1998; Kammandel et al., 1999; Plaza et al., 1999a; Xu et al., 1999; Tyas et al., 2006), involving multiple transcription factors, such as POU factor Brn-3B, TFCP2, SP1, the basic helix-loop-helix transcription factor NeuroD/BETA2, CCCTC binding factor CTCF, PPARgamma (Plaza et al., 1999b; Zheng et al., 2001; Schinner et al., 2002; Marsich et al., 2003; Li et al., 2006; Wu et al., 2006). PAX6 expression is also regulated by a long range downstream enhancer (Kleinjan et al., 2006) and is under autoregulation (Grocott et al., 2007) and post modification by HIPK2 and protein phosphatase 1 (Kim et al., 2006; Yan et al., 2007). A promoter-associated polymorphic repeat was found to modulate PAX6 expression in human brain (Okladnova et al., 1998b).
Function Loss of Pax6 function in rodent mutant and knock-out model revealed that Pax6 is a key regulator of a multitude of developmental processes of sensory system, including eye, nasal and olfactory (Hill et al., 1991; Grindley et al., 1995; Quinn et al., 1996; van Raamsdonk and Tilghman, 2000; Singh et al., 2002; van Heyningen and Williamson, 2002; Collinson et al., 2003; Davis et al., 2003; Brill et al., 2008), CNS (Matsuo et al., 1993; Schmahl et al., 1993; Stoykova et al., 1996; Grindley et al., 1997; Osumi et al., 1997; Mastick et al., 1997; Warren and Price, 1997; Gotz et al., 1998; Sun et al., 1998; Engelkamp et al., 1999; Kawano et al., 1999; Pratt et al., 2000; Stoykova et al., 2000; Estivill-Torrus et al., 2002; Pratt et al., 2002; Talamillo et al., 2003; Quinn et al., 2007), pituitary (Bentley et al., 1999; Kioussi et al., 1999) and pancreas (Sander et al., 1997; St-Onge et al., 1997; Dohrmann et al., 2000; Zhang et al., 2003). Pax6 function in development of fundamental sensory processes and central nervous system, particularly of the photoreceptive organ, are remarkably conserved in evolution (Halder et al., 1995; Gehring et al., 2005). PAX6 funciton in development were found to be under control of Shh, notch and EGFR signaling (Ericson et al., 1997; Kumar and Moses, 2001; Onuma et al., 2002; Li and Lu, 2005), essential for neural stem cell proliferation, multipotency, and neurogenesis in many regions of the central nervous system (Warren et al., 1999; Bishop et al., 2000; Toresson et al., 2000; Marquardt et al., 2001; Yamasaki et al., 2001; Yun et al., 2001; Estivill-Torrus et al., 2002; Heins et al., 2002; Simpson and Price, 2002; Tyas et al., 2003; Collinson et al., 2004; Haubst et al., 2004; Nomura and Osumi, 2004; Schuurmans et al., 2004; Maekawa et al., 2005; Bel-Vialar et al., 2007; Duparc et al., 2007; Quinn et al., 2007; Canto-Soler et al., 2008; Oron-Karni et al., 2008; Osumi et al., 2008), and appears to control the balance between neural stem cell self-renewal and neurogenesis under a dose-dependent manner (Sansom et al., 2009).
PAX6 binds as a monomer to relatively long (15-22 bp) DNA binding sites, and the 14 aa insertion in the paired domain allows different binding affinity to DNA sequences between PAX6a and PAX6b (Epstein et al., 1994a; Epstein et al., 1994b). Through binding to different DNA sequences via usage of various DNA binding motifs alone or in combination, PAX6 controls the expression of various downstream target genes involved in complex gene regulatory networks for cell proliferation, adhesion, migration, and neurogenesis (Schmahl et al., 1993; Caric et al., 1997; Sander et al., 1997; Sax et al., 1997; Tang et al., 1997; Duncan et al., 1998; Beimesche et al., 1999; Meech et al., 1999; Singh et al., 2000; Sivak et al., 2000; Zhou et al., 2000; Chauhan et al., 2002; Mishra et al., 2002; Skala-Rubinson et al., 2002; Zhou et al., 2002; Andrews and Mastick, 2003; Davis et al., 2003; Horie et al., 2003; Tyas et al., 2003; Cvekl et al., 2004; Grinchuk et al., 2005; Mayes et al., 2006; Holm et al., 2007; Tuoc and Stoykova, 2008). Not only reduced, but also increases level of PAX6 gene dosage also cause defects in developmental processes that are sensitive to PAX6 dosage, including eye organogenesis and corticogenesis (Schedl et al., 1996; Berger et al., 2007; Manuel et al., 2007).
Homology PAX6 shares homology through the conserved paired box domain with the other members of the nine PAX gene family.
Germinal Heterozygous intragenic mutation of PAX6, that causes loss of function of one copy of the PAX6 gene, is the cause of aniridia syndrome (Ton et al., 1991; Glaser et al., 1992; Prosser and van Heyningen, 1998; Robinson et al., 2008; Hingorani et al., 2009; MRC Human Genetics Unit) and cerebral malformation, olfactory dysfunction, absence of the pineal gland and unilateral polymicrogyria (Sisodiya et al., 2001; Free et al., 2003; Mitchell et al., 2003; Bamiou et al., 2007a; Bamiou et al., 2007b).
PAX6 3' deletion also results in aniridia, autism and mental retardation (Davis et al., 2008).
Note The expression level of PAX6 in human glioma cell lines was shown to be negatively associated with the degree of tumorigenicity. PAX6 expression level is lower in glioblastoma compared to the adjacent normal tissue and to the anaplastic astrocytoma previously formed in the same patient (Zhou et al., 2003). Ectopic expression of PAX6 in glioma cell lines suppressed cell anchorage independent growth, ability to survive under oxidative stress induced by cell detachment, ability to invade partially by suppression of MMP2 gene expression, ability to induce angiogenesis by initiating a new signaling pathway independent of PI3K/Akt-HIF1A signaling to suppress VEGFA, and overall tumor growth after intracranial implantation in immunocompromised mouse brain (Zhou et al., 2005; Mayes et al., 2006; Chang et al., 2007; Zhou et al., 2009). Mutation analysis for PAX6 in gliomas failed to identify PAX6 mutation in its coding and regulating regions, suggesting involvement of epigenetic mechanisms in the silencing of PAX6 in glioma (Pinto et al., 2007). PAX6 expression is activated in glioma cell line with re-introduction of a normal ch.10, suggesting that PAX6 is regulated by a gene(s) on ch.10 (Zhou et al., 2005).
Prognosis PAX6 is a factor related to a longer survival prognosis for astrocytic gliomas (Zhou et al., 2003).
Note PAX6 is expressed in pancreatic adenocarcinoma and is downregulated during induction of terminal differentiation (Lang et al., 2008). In pancreatic carcinoma cell lines, PAX6 bind directly to an enhancer element in the MET promoter and activate the expression of the MET gene (Mascarenhas et al., 2009).
Note Methylation of PAX6-promoters is increased in early bladder cancer and in normal mucosa adjacent to pTa tumours (Hellwinkel et al., 2008).
Note PAX6 gene is methylated in FAP-related carcinoma. Patients with familial adenomatous polyposis (FAP) have a high risk of developing duodenal carcinomas (Berkhout et al., 2007).
Note WAGR syndrome can have aniridia due to deletion of chromosome 11 including PAX6 (Gronskov et al., 2001; Chao et al., 2003). However, PAX6 mutation is only found in aniridia patient, not WAGR syndrome associated anomalies (Robinson et al., 2008).
R-cadherin is a Pax6-regulated, growth-promoting cue for pioneer axons.
J Neurosci. 2003 Oct 29;23(30):9873-80.
Auditory and verbal working memory deficits in a child with congenital aniridia due to a PAX6 mutation.
Bamiou DE, Campbell NG, Musiek FE, Taylor R, Chong WK, Moore A, van Heyningen V, Free S, Sisodiya S, Luxon LM.
Int J Audiol. 2007a Apr;46(4):196-202.
Auditory interhemispheric transfer deficits, hearing difficulties, and brain magnetic resonance imaging abnormalities in children with congenital aniridia due to PAX6 mutations.
Bamiou DE, Free SL, Sisodiya SM, Chong WK, Musiek F, Williamson KA, van Heyningen V, Moore AT, Gadian D, Luxon LM.
Arch Pediatr Adolesc Med. 2007b May;161(5):463-9.
Tissue-specific transcriptional activity of a pancreatic islet cell-specific enhancer sequence/Pax6-binding site determined in normal adult tissues in vivo using transgenic mice.
Beimesche S, Neubauer A, Herzig S, Grzeskowiak R, Diedrich T, Cierny I, Scholz D, Alejel T, Knepel W.
The on/off of Pax6 controls the tempo of neuronal differentiation in the developing spinal cord.
Bel-Vialar S, Medevielle F, Pituello F.
Dev Biol. 2007 May 15;305(2):659-73. Epub 2007 Feb 16.
Pax6 is implicated in murine pituitary endocrine function.
Bentley CA, Zidehsarai MP, Grindley JC, Parlow AF, Barth-Hall S, Roberts VJ.
Conditional activation of Pax6 in the developing cortex of transgenic mice causes progenitor apoptosis.
Berger J, Berger S, Tuoc TC, D'Amelio M, Cecconi F, Gorski JA, Jones KR, Gruss P, Stoykova A.
Development. 2007 Apr;134(7):1311-22. Epub 2007 Feb 28.
Berkhout M, Nagtegaal ID, Cornelissen SJ, Dekkers MM, van de Molengraft FJ, Peters WH, Nagengast FM, van Krieken JH, Jeuken JW.
Mod Pathol. 2007 Dec;20(12):1253-62. Epub 2007 Sep 14.
Regulation of area identity in the mammalian neocortex by Emx2 and Pax6.
Bishop KM, Goudreau G, O'Leary DD.
Brill MS, Snapyan M, Wohlfrom H, Ninkovic J, Jawerka M, Mastick GS, Ashery-Padan R, Saghatelyan A, Berninger B, Gotz M.
J Neurosci. 2008 Jun 18;28(25):6439-52.
Transcription factors CTCF and Pax6 are segregated to different cell types during retinal cell differentiation.
Canto-Soler MV, Huang H, Romero MS, Adler R.
Determination of the migratory capacity of embryonic cortical cells lacking the transcription factor Pax-6.
Caric' D, Gooday D, Hill RE, McConnell SK, Price DJ.
PAX6 increases glioma cell susceptibility to detachment and oxidative stress.
Chang JY, Hu Y, Siegel E, Stanley L, Zhou YH.
J Neurooncol. 2007 Aug;84(1):9-19. Epub 2007 Feb 21.
Missense mutations in the DNA-binding region and termination codon in PAX6.
Chao LY, Mishra R, Strong LC, Saunders GF.
A comparative cDNA microarray analysis reveals a spectrum of genes regulated by Pax6 in mouse lens.
Chauhan BK, Reed NA, Yang Y, Cermak L, Reneker L, Duncan MK, Cvekl A.
Corneal development, limbal stem cell function, and corneal epithelial cell migration in the Pax6(+/-) mouse.
Collinson JM, Chanas SA, Hill RE, West JD.
Invest Ophthalmol Vis Sci. 2004 Apr;45(4):1101-8.
Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens.
Cvekl A, Yang Y, Chauhan BK, Cveklova K.
Requirement for Pax6 in corneal morphogenesis: a role in adhesion.
Davis J, Duncan MK, Robison WG Jr, Piatigorsky J.
J Cell Sci. 2003 Jun 1;116(Pt 11):2157-67. Epub 2003 Apr 8.
Role of Olf-1 and Pax-6 transcription factors in neurodevelopment.
J Neurosci. 1996 Aug 15;16(16):5082-94.
Pax6 3' deletion results in aniridia, autism and mental retardation.
Davis LK, Meyer KJ, Rudd DS, Librant AL, Epping EA, Sheffield VC, Wassink TH.
Hum Genet. 2008 May;123(4):371-8. Epub 2008 Mar 6.
Pax genes and the differentiation of hormone-producing endocrine cells in the pancreas.
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Duncan MK, Haynes JI 2nd, Cvekl A, Piatigorsky J.
Mol Cell Biol. 1998 Sep;18(9):5579-86.
Pax6 controls the proliferation rate of neuroepithelial progenitors from the mouse optic vesicle.
Duparc RH, Abdouh M, David J, Lepine M, Tetreault N, Bernier G.
Dev Biol. 2007 Jan 15;301(2):374-87. Epub 2006 Nov 10.
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Engelkamp D, Rashbass P, Seawright A, van Heyningen V.
Identification of a Pax paired domain recognition sequence and evidence for DNA-dependent conformational changes.
Epstein J, Cai J, Glaser T, Jepeal L, Maas R.
J Biol Chem. 1994a Mar 18;269(11):8355-61.
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Genes Dev. 1994b Sep 1;8(17):2022-34.
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Pax6 is required to regulate the cell cycle and the rate of progression from symmetrical to asymmetrical division in mammalian cortical progenitors.
Estivill-Torrus G, Pearson H, van Heyningen V, Price DJ, Rashbass P.
Quantitative MR image analysis in subjects with defects in the PAX6 gene.
Free SL, Mitchell TN, Williamson KA, Churchill AJ, Shorvon SD, Moore AT, van Heyningen V, Sisodiya SM.
New perspectives on eye development and the evolution of eyes and photoreceptors.
J Hered. 2005 May-Jun;96(3):171-84. Epub 2005 Jan 13.
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Glaser T, Walton DS, Maas RL.
Pax6 controls radial glia differentiation in the cerebral cortex.
Gotz M, Stoykova A, Gruss P.
The Optimedin gene is a downstream target of Pax6.
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J Biol Chem. 2005 Oct 21;280(42):35228-37. Epub 2005 Aug 22.
Disruption of PAX6 function in mice homozygous for the Pax6Sey-1Neu mutation produces abnormalities in the early development and regionalization of the diencephalon.
Grindley JC, Hargett LK, Hill RE, Ross A, Hogan BL.
The MH1 domain of Smad3 interacts with Pax6 and represses autoregulation of the Pax6 P1 promoter.
Grocott T, Frost V, Maillard M, Johansen T, Wheeler GN, Dawes LJ, Wormstone IM, Chantry A.
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Radial glia-like cells persist in the adult rat brain.
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New perspectives on eye evolution.
Halder G, Callaerts P, Gehring WJ.
Curr Opin Genet Dev. 1995 Oct;5(5):602-9.
Molecular dissection of Pax6 function: the specific roles of the paired domain and homeodomain in brain development.
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Development. 2004 Dec;131(24):6131-40. Epub 2004 Nov 17.
Glial cells generate neurons: the role of the transcription factor Pax6.
Heins N, Malatesta P, Cecconi F, Nakafuku M, Tucker KL, Hack MA, Chapouton P, Barde YA, Gotz M.
Methylation of the TPEF- and PAX6-promoters is increased in early bladder cancer and in normal mucosa adjacent to pTa tumours.
Hellwinkel OJ, Kedia M, Isbarn H, Budaus L, Friedrich MG.
BJU Int. 2008 Mar;101(6):753-7. Epub 2007 Dec 7.
Mouse small eye results from mutations in a paired-like homeobox-containing gene.
Hill RE, Favor J, Hogan BL, Ton CC, Saunders GF, Hanson IM, Prosser J, Jordan T, Hastie ND, van Heyningen V.
Detailed ophthalmologic evaluation of 43 individuals with PAX6 mutations.
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Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2581-90. Epub 2009 Feb 14.
Loss- and gain-of-function analyses reveal targets of Pax6 in the developing mouse telencephalon.
Holm PC, Mader MT, Haubst N, Wizenmann A, Sigvardsson M, Gotz M.
Mol Cell Neurosci. 2007 Jan;34(1):99-119. Epub 2006 Dec 8.
Subpial neuronal migration in the medulla oblongata of Pax-6-deficient rats.
Horie M, Sango K, Takeuchi K, Honma S, Osumi N, Kawamura K, Kawano H.
Eur J Neurosci. 2003 Jan;17(1):49-57.
Distinct cis-essential modules direct the time-space pattern of the Pax6 gene activity.
Kammandel B, Chowdhury K, Stoykova A, Aparicio S, Brenner S, Gruss P.
Dev Biol. 1999 Jan 1;205(1):79-97.
Pax-6 is required for thalamocortical pathway formation in fetal rats.
Kawano H, Fukuda T, Kubo K, Horie M, Uyemura K, Takeuchi K, Osumi N, Eto K, Kawamura K.
J Comp Neurol. 1999 May 31;408(2):147-60.
Phosphorylation and transactivation of Pax6 by homeodomain-interacting protein kinase 2.
Kim EA, Noh YT, Ryu MJ, Kim HT, Lee SE, Kim CH, Lee C, Kim YH, Choi CY.
J Biol Chem. 2006 Mar 17;281(11):7489-97. Epub 2006 Jan 9.
Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development.
Kioussi C, O'Connell S, St-Onge L, Treier M, Gleiberman AS, Gruss P, Rosenfeld MG.
Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14378-82.
Long-range downstream enhancers are essential for Pax6 expression.
Kleinjan DA, Seawright A, Mella S, Carr CB, Tyas DA, Simpson TI, Mason JO, Price DJ, van Heyningen V.
Dev Biol. 2006 Nov 15;299(2):563-81. Epub 2006 Aug 30.
Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb.
Kohwi M, Osumi N, Rubenstein JL, Alvarez-Buylla A.
J Neurosci. 2005 Jul 27;25(30):6997-7003.
EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification.
PAX6 is expressed in pancreatic adenocarcinoma and is downregulated during induction of terminal differentiation.
Lang D, Mascarenhas JB, Powell SK, Halegoua J, Nelson M, Ruggeri BA.
Epidermal growth factor-induced proliferation requires down-regulation of Pax6 in corneal epithelial cells.
J Biol Chem. 2005 Apr 1;280(13):12988-95. Epub 2005 Jan 19.
Pax6 regulation in retinal cells by CCCTC binding factor.
Li T, Lu Z, Lu L.
Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5218-26.
Pax6 is required for production and maintenance of progenitor cells in postnatal hippocampal neurogenesis.
Maekawa M, Takashima N, Arai Y, Nomura T, Inokuchi K, Yuasa S, Osumi N.
Controlled overexpression of Pax6 in vivo negatively autoregulates the Pax6 locus, causing cell-autonomous defects of late cortical progenitor proliferation with little effect on cortical arealization.
Manuel M, Georgala PA, Carr CB, Chanas S, Kleinjan DA, Martynoga B, Mason JO, Molinek M, Pinson J, Pratt T, Quinn JC, Simpson TI, Tyas DA, van Heyningen V, West JD, Price DJ.
Development. 2007 Feb;134(3):545-55. Epub 2007 Jan 3.
Pax6 is required for the multipotent state of retinal progenitor cells.
Marquardt T, Ashery-Padan R, Andrejewski N, Scardigli R, Guillemot F, Gruss P.
The PAX6 gene is activated by the basic helix-loop-helix transcription factor NeuroD/BETA2.
Marsich E, Vetere A, Di Piazza M, Tell G, Paoletti S.
Biochem J. 2003 Dec 15;376(Pt 3):707-15.
PAX6 is expressed in pancreatic cancer and actively participates in cancer progression through the activation of the met tyrosine kinase receptor gene.
Mascarenhas JB, Young KP, Littlejohn EL, Yoo BK, Salgia R, Lang D.
Pax-6 functions in boundary formation and axon guidance in the embryonic mouse forebrain.
Mastick GS, Davis NM, Andrew GL, Easter SS Jr.
A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells.
Matsuo T, Osumi-Yamashita N, Noji S, Ohuchi H, Koyama E, Myokai F, Matsuo N, Taniguchi S, Doi H, Iseki S, et al.
PAX6 suppresses the invasiveness of glioblastoma cells and the expression of the matrix metalloproteinase-2 gene.
Mayes DA, Hu Y, Teng Y, Siegel E, Wu X, Panda K, Tan F, Yung WK, Zhou YH.
Cancer Res. 2006 Oct 15;66(20):9809-17.
A binding site for homeodomain and Pax proteins is necessary for L1 cell adhesion molecule gene expression by Pax-6 and bone morphogenetic proteins.
Meech R, Kallunki P, Edelman GM, Jones FS.
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2420-5.
PAX6, paired domain influences sequence recognition by the homeodomain.
Mishra R, Gorlov IP, Chao LY, Singh S, Saunders GF.
J Biol Chem. 2002 Dec 20;277(51):49488-94. Epub 2002 Oct 17.
Polymicrogyria and absence of pineal gland due to PAX6 mutation.
Mitchell TN, Free SL, Williamson KA, Stevens JM, Churchill AJ, Hanson IM, Shorvon SD, Moore AT, van Heyningen V, Sisodiya SM.
Expression of the transcription factor Pax 6 in the adult rat dentate gyrus.
Nacher J, Varea E, Blasco-Ibanez JM, Castillo-Gomez E, Crespo C, Martinez-Guijarro FJ, McEwen BS.
J Neurosci Res. 2005 Sep 15;81(6):753-61.
Misrouting of mitral cell progenitors in the Pax6/small eye rat telencephalon.
Development. 2004 Feb;131(4):787-96. Epub 2004 Jan 21.
A promoter-associated polymorphic repeat modulates PAX-6 expression in human brain.
Okladnova O, Syagailo YV, Tranitz M, Stober G, Riederer P, Mossner R, Lesch KP.
Biochem Biophys Res Commun. 1998b Jul 20;248(2):402-5.
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Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2020-5. Epub 2002 Feb 12.
Dual requirement for Pax6 in retinal progenitor cells.
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Development. 2008 Dec;135(24):4037-47. Epub 2008 Nov 12.
Pax-6 is involved in the specification of hindbrain motor neuron subtype.
Osumi N, Hirota A, Ohuchi H, Nakafuku M, Iimura T, Kuratani S, Fujiwara M, Noji S, Eto K.
Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator.
Osumi N, Shinohara H, Numayama-Tsuruta K, Maekawa M.
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BMC Dev Biol. 2005 Jul 19;5:13.
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Plaza S, Saule S, Dozier C.
Dev Genes Evol. 1999b Mar;209(3):165-73.
Disruption of early events in thalamocortical tract formation in mice lacking the transcription factors Pax6 or Foxg1.
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J Neurosci. 2002 Oct 1;22(19):8523-31.
A role for Pax6 in the normal development of dorsal thalamus and its cortical connections.
Pratt T, Vitalis T, Warren N, Edgar JM, Mason JO, Price DJ.
Prosser J, van Heyningen V.
Pax6 controls cerebral cortical cell number by regulating exit from the cell cycle and specifies cortical cell identity by a cell autonomous mechanism.
Quinn JC, Molinek M, Martynoga BS, Zaki PA, Faedo A, Bulfone A, Hevner RF, West JD, Price DJ.
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Multiple functions for Pax6 in mouse eye and nasal development.
Quinn JC, West JD, Hill RE.
Genes Dev. 1996 Feb 15;10(4):435-46.
Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia.
Robinson DO, Howarth RJ, Williamson KA, van Heyningen V, Beal SJ, Crolla JA.
Am J Med Genet A. 2008 Mar 1;146A(5):558-69.
Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development.
Sander M, Neubuser A, Kalamaras J, Ee HC, Martin GR, German MS.
Genes Dev. 1997 Jul 1;11(13):1662-73.
Sansom SN, Griffiths DS, Faedo A, Kleinjan DJ, Ruan Y, Smith J, van Heyningen V, Rubenstein JL, Livesey FJ.
PLoS Genet. 2009 Jun;5(6):e1000511. Epub 2009 Jun 12.
Transcriptional regulation of the mouse alpha A-crystallin gene: binding of USF to the -7/+5 region.
Sax CM, Cvekl A, Piatigorsky J.
Influence of PAX6 gene dosage on development: overexpression causes severe eye abnormalities.
Schedl A, Ross A, Lee M, Engelkamp D, Rashbass P, van Heyningen V, Hastie ND.
Repression of glucagon gene transcription by peroxisome proliferator-activated receptor gamma through inhibition of Pax6 transcriptional activity.
Schinner S, Dellas C, Schroder M, Heinlein CA, Chang C, Fischer J, Knepel W.
J Biol Chem. 2002 Jan 18;277(3):1941-8. Epub 2001 Nov 13.
Defects of neuronal migration and the pathogenesis of cortical malformations are associated with Small eye (Sey) in the mouse, a point mutation at the Pax-6-locus.
Schmahl W, Knoedlseder M, Favor J, Davidson D.
Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways.
Schuurmans C, Armant O, Nieto M, Stenman JM, Britz O, Klenin N, Brown C, Langevin LM, Seibt J, Tang H, Cunningham JM, Dyck R, Walsh C, Campbell K, Polleux F, Guillemot F.
EMBO J. 2004 Jul 21;23(14):2892-902. Epub 2004 Jul 1.
Pax6; a pleiotropic player in development.
Iris hypoplasia in mice that lack the alternatively spliced Pax6(5a) isoform.
Singh S, Mishra R, Arango NA, Deng JM, Behringer RR, Saunders GF.
Proc Natl Acad Sci U S A. 2002 May 14;99(10):6812-5. Epub 2002 Apr 30.
Modulation of PAX6 homeodomain function by the paired domain.
Singh S, Stellrecht CM, Tang HK, Saunders GF.
J Biol Chem. 2000 Jun 9;275(23):17306-13.
PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans.
Sisodiya SM, Free SL, Williamson KA, Mitchell TN, Willis C, Stevens JM, Kendall BE, Shorvon SD, Hanson IM, Moore AT, van Heyningen V.
Pax-6 expression and activity are induced in the reepithelializing cornea and control activity of the transcriptional promoter for matrix metalloproteinase gelatinase B.
Sivak JM, Mohan R, Rinehart WB, Xu PX, Maas RL, Fini ME.
Dev Biol. 2000 Jun 1;222(1):41-54.
Novel target sequences for Pax-6 in the brain-specific activating regions of the rat aldolase C gene.
Skala-Rubinson H, Vinh J, Labas V, Kahn A, Phan DT.
J Biol Chem. 2002 Dec 6;277(49):47190-6. Epub 2002 Oct 4.
Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas.
St-Onge L, Sosa-Pineda B, Chowdhury K, Mansouri A, Gruss P.
Pax6 modulates the dorsoventral patterning of the mammalian telencephalon.
Stoykova A, Treichel D, Hallonet M, Gruss P.
J Neurosci. 2000 Nov 1;20(21):8042-50.
Pax6 influences the time and site of origin of glial precursors in the ventral neural tube.
Sun T, Pringle NP, Hardy AP, Richardson WD, Smith HK.
Mol Cell Neurosci. 1998 Nov;12(4-5):228-39.
Pax6 regulates regional development and neuronal migration in the cerebral cortex.
Talamillo A, Quinn JC, Collinson JM, Caric D, Price DJ, West JD, Hill RE.
Dev Biol. 2003 Mar 1;255(1):151-63.
Functional analysis of paired box missense mutations in the PAX6 gene.
Tang HK, Chao LY, Saunders GF.
Hum Mol Genet. 1997 Mar;6(3):381-6.
Expression pattern of PAX3 and PAX6 genes during human embryogenesis.
Int J Dev Biol. 1999 Sep;43(6):501-8.
Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region.
Ton CC, Hirvonen H, Miwa H, Weil MM, Monaghan P, Jordan T, van Heyningen V, Hastie ND, Meijers-Heijboer H, Drechsler M, et al.
Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2.
Toresson H, Potter SS, Campbell K.
Er81 is a downstream target of Pax6 in cortical progenitors.
BMC Dev Biol. 2008 Feb 28;8:23.
Pax6 regulates cell adhesion during cortical development.
Tyas DA, Pearson H, Rashbass P, Price DJ.
Functional conservation of Pax6 regulatory elements in humans and mice demonstrated with a novel transgenic reporter mouse.
Tyas DA, Simpson TI, Carr CB, Kleinjan DA, van Heyningen V, Mason JO, Price DJ.
BMC Dev Biol. 2006 May 4;6:21.
Pax-6, a murine paired box gene, is expressed in the developing CNS.
The transcription factor, Pax6, is required for cell proliferation and differentiation in the developing cerebral cortex.
Warren N, Caric D, Pratt T, Clausen JA, Asavaritikrai P, Mason JO, Hill RE, Price DJ.
Roles of Pax-6 in murine diencephalic development.
A highly conserved lens transcriptional control element from the Pax-6 gene.
Williams SC, Altmann CR, Chow RL, Hemmati-Brivanlou A, Lang RA.
Effect of CTCF-binding motif on regulation of PAX6 transcription.
Wu D, Li T, Lu Z, Dai W, Xu M, Lu L.
Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2422-9.
Regulation of Pax6 expression is conserved between mice and flies.
Xu PX, Zhang X, Heaney S, Yoon A, Michelson AM, Maas RL.
PAX6 intronic sequence targets expression to the spinal cord.
Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum.
Yamasaki T, Kawaji K, Ono K, Bito H, Hirano T, Osumi N, Kengaku M.
Protein phosphatase-1 modulates the function of Pax-6, a transcription factor controlling brain and eye development.
Yan Q, Liu WB, Qin J, Liu J, Chen HG, Huang X, Chen L, Sun S, Deng M, Gong L, Li Y, Zhang L, Liu Y, Feng H, Xiao Y, Liu Y, Li DW.
J Biol Chem. 2007 May 11;282(19):13954-65. Epub 2007 Mar 20.
Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon.
Yun K, Potter S, Rubenstein JL.
Cre-loxp fate-mapping of Pax6 enhancer active retinal and pancreatic progenitors.
Zhang X, Heaney S, Maas RL.
Activation of the human PAX6 gene through the exon 1 enhancer by transcription factors SEF and Sp1.
Zheng JB, Zhou YH, Maity T, Liao WS, Saunders GF.
Nucleic Acids Res. 2001 Oct 1;29(19):4070-8.
A novel Pax-6 binding site in rodent B1 repetitive elements: coevolution between developmental regulation and repeated elements?
Zhou Y, Zheng JB, Gu X, Li W, Saunders GF.
PAX6 suppression of glioma angiogenesis and the expression of vascular endothelial growth factor A.
Zhou YH, Hu Y, Mayes D, Siegel E, Kim JG, Mathews MS, Hsu N, Eskander D, Yu O, Tromberg BJ, Linskey ME.
The expression of PAX6, PTEN, vascular endothelial growth factor, and epidermal growth factor receptor in gliomas: relationship to tumor grade and survival.
Zhou YH, Tan F, Hess KR, Yung WK.
Clin Cancer Res. 2003 Aug 15;9(9):3369-75.
PAX6 suppresses growth of human glioblastoma cells.
Zhou YH, Wu X, Tan F, Shi YX, Glass T, Liu TJ, Wathen K, Hess KR, Gumin J, Lang F, Yung WK.
Novel PAX6 binding sites in the human genome and the role of repetitive elements in the evolution of gene regulation.
Zhou YH, Zheng JB, Gu X, Saunders GF, Yung WK.
van Heyningen V, Williamson KA.
van Raamsdonk CD, Tilghman SM.
Atlas Genet Cytogenet Oncol Haematol. 2010;14(7):645-651.

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