Gene Symbol: Pax6
Description: paired box 6
Alias: paired box protein Pax-6, oculorhombin, paired box gene 6, paired box homeotic gene 6
Species: rat
Products:     Pax6

Top Publications

  1. Baumer N, Marquardt T, Stoykova A, Spieler D, Treichel D, Ashery Padan R, et al. Retinal pigmented epithelium determination requires the redundant activities of Pax2 and Pax6. Development. 2003;130:2903-15 pubmed
    The transcription factors Pax2 and Pax6 are co-expressed in the entire optic vesicle (OV) prior and concomitant with the establishment of distinct neuroretinal, retinal, pigmented-epithelial and optic-stalk progenitor domains, suggesting ..
  2. Jiang B, Yap M, Leung K, Ng P, Fung W, Lam W, et al. PAX6 haplotypes are associated with high myopia in Han chinese. PLoS ONE. 2011;6:e19587 pubmed publisher
    The paired box 6 (PAX6) gene is considered as a master gene for eye development...
  3. Andrews G, Mastick G. R-cadherin is a Pax6-regulated, growth-promoting cue for pioneer axons. J Neurosci. 2003;23:9873-80 pubmed
    The transcription factor Pax6 has been implicated in two processes that may be related in brain development: establishment of regional cell adhesion properties and axon guidance...
  4. Osumi N, Hirota A, Ohuchi H, Nakafuku M, Iimura T, Kuratani S, et al. Pax-6 is involved in the specification of hindbrain motor neuron subtype. Development. 1997;124:2961-72 pubmed
    ..These results strongly suggest that Pax-6 is involved in the specification of subtypes of hindbrain motor neurons, presumably through the regulation of Islet-2 and Wnt-7b expression. ..
  5. Kioussi C, O Connell S, St Onge L, Treier M, Gleiberman A, Gruss P, et al. Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development. Proc Natl Acad Sci U S A. 1999;96:14378-82 pubmed
    b>Pax6, a highly conserved member of the paired homeodomain transcription factor family that plays essential roles in ocular, neural, and pancreatic development and effects asymmetric transient dorsal expression during pituitary development,..
  6. Arai Y, Funatsu N, Numayama Tsuruta K, Nomura T, Nakamura S, Osumi N. Role of Fabp7, a downstream gene of Pax6, in the maintenance of neuroepithelial cells during early embryonic development of the rat cortex. J Neurosci. 2005;25:9752-61 pubmed
    b>Pax6 is a transcription factor with key functional roles in the developing brain...
  7. Duncan M, Kozmik Z, Cveklova K, Piatigorsky J, Cvekl A. Overexpression of PAX6(5a) in lens fiber cells results in cataract and upregulation of (alpha)5(beta)1 integrin expression. J Cell Sci. 2000;113 ( Pt 18):3173-85 pubmed
    The PAX6 gene, a key regulator of eye development, produces two major proteins that differ in paired domain structure: PAX6 and PAX6(5a)...
  8. Lovicu F, Steven P, Saika S, McAvoy J. Aberrant lens fiber differentiation in anterior subcapsular cataract formation: a process dependent on reduced levels of Pax6. Invest Ophthalmol Vis Sci. 2004;45:1946-53 pubmed
    ..ASC was also examined in lenses of mice haploinsufficient for Pax6, as well as in human biopsy specimens...
  9. 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
    ..These specific alterations were not seen when the mutated form of Six3 cDNA was used in similar experimental approaches, indicating that Six3 interaction with Groucho proteins plays an essential role in vertebrate eye development. ..

More Information


  1. Kroll T, O Leary D. Ventralized dorsal telencephalic progenitors in Pax6 mutant mice generate GABA interneurons of a lateral ganglionic eminence fate. Proc Natl Acad Sci U S A. 2005;102:7374-9 pubmed
    The transcription factor Pax6 is expressed by progenitors in the ventricular zone (VZ) of dorsal telencephalon (dTel), which generate all cortical glutamatergic neurons, but not by progenitors in the medial ganglionic eminence (MGE), ..
  2. Yamasaki T, Kawaji K, Ono K, Bito H, Hirano T, Osumi N, et al. Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum. Development. 2001;128:3133-44 pubmed
    ..In Pax6 mutant rats (rSey2/rSey2), granule cells in the external germinal layer (EGL) fail to form parallel fiber axons and ..
  3. Han W, Leung K, Fung W, Mak J, Li Y, Yap M, et al. Association of PAX6 polymorphisms with high myopia in Han Chinese nuclear families. Invest Ophthalmol Vis Sci. 2009;50:47-56 pubmed publisher
    The paired box 6 (PAX6) gene is critical to eye development. Based on prior linkage evidence, this study was conducted to investigate the association of PAX6 polymorphisms with high myopia in a Han Chinese population.
  4. Engelkamp D, Rashbass P, Seawright A, van Heyningen V. Role of Pax6 in development of the cerebellar system. Development. 1999;126:3585-96 pubmed
    ..Here we show that Pax6, a key regulator in CNS and eye development, is strongly expressed in rhombic lip and in cells migrating away from ..
  5. Cai F, Zhu J, Chen W, Ke T, Wang F, Tu X, et al. A novel PAX6 mutation in a large Chinese family with aniridia and congenital cataract. Mol Vis. 2010;16:1141-5 pubmed
    ..To identify the disease-causing gene in a four-generation Chinese family affected with autosomal dominant aniridia and cataract...
  6. Ericson J, Rashbass P, Schedl A, Brenner Morton S, Kawakami A, van Heyningen V, et al. Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell. 1997;90:169-80 pubmed
    ..establishing different progenitor cell populations in the ventral neural tube that are defined by the expression of Pax6 and Nkx2.2...
  7. Asami M, Pilz G, Ninkovic J, Godinho L, Schroeder T, Huttner W, et al. The role of Pax6 in regulating the orientation and mode of cell division of progenitors in the mouse cerebral cortex. Development. 2011;138:5067-78 pubmed publisher
    ..Successful brain development requires tight regulation of sequential symmetric and asymmetric cell division. Although Pax6 is known to exert multiple roles in the developing nervous system, its role in the regulation of cell division is ..
  8. Matsuo T, Osumi Yamashita N, Noji S, Ohuchi H, Koyama E, Myokai F, et al. A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells. Nat Genet. 1993;3:299-304 pubmed
  9. Osumi N, Shinohara H, Numayama Tsuruta K, Maekawa M. Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator. Stem Cells. 2008;26:1663-72 pubmed publisher
    b>Pax6 is a highly conserved transcription factor among vertebrates and is important in various developmental processes in the central nervous system (CNS), including patterning of the neural tube, migration of neurons, and formation of ..
  10. Maekawa M, Takashima N, Arai Y, Nomura T, Inokuchi K, Yuasa S, et al. Pax6 is required for production and maintenance of progenitor cells in postnatal hippocampal neurogenesis. Genes Cells. 2005;10:1001-14 pubmed
    ..b>Pax6 transcription factor is a key player for patterning the brain and promoting embryonic neurogenesis, and is also ..
  11. Vincent M, Gallai R, Olivier D, Speeg Schatz C, Flament J, Calvas P, et al. Variable phenotype related to a novel PAX 6 mutation (IVS4+5G>C) in a family presenting congenital nystagmus and foveal hypoplasia. Am J Ophthalmol. 2004;138:1016-21 pubmed
    Several ocular defects have been identified as a consequence of the PAX6 gene mutations...
  12. Horie M, Sango K, Takeuchi K, Honma S, Osumi N, Kawamura K, et al. Subpial neuronal migration in the medulla oblongata of Pax-6-deficient rats. Eur J Neurosci. 2003;17:49-57 pubmed
  13. Takahashi M, Osumi N. Pax6 regulates specification of ventral neurone subtypes in the hindbrain by establishing progenitor domains. Development. 2002;129:1327-38 pubmed
    ..b>Pax6 is a HD protein that has previously been shown to be involved in the differentiation of the hindbrain somatic (SM) ..
  14. 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
    The Pax6 transcription factor plays a key role in ocular development of vertebrates and invertebrates...
  15. Hevner R, Miyashita Lin E, Rubenstein J. Cortical and thalamic axon pathfinding defects in Tbr1, Gbx2, and Pax6 mutant mice: evidence that cortical and thalamic axons interact and guide each other. J Comp Neurol. 2002;447:8-17 pubmed
    ..of transcription factor genes expressed specifically in the cortex (Tbr1), the dorsal thalamus (Gbx2), or both (Pax6)...
  16. Tuoc T, Stoykova A. Trim11 modulates the function of neurogenic transcription factor Pax6 through ubiquitin-proteosome system. Genes Dev. 2008;22:1972-86 pubmed publisher
    The transcription factor Pax6 is an important developmental regulator. Spatiotemporal control of Pax6 expression during embryogenesis is crucial for regulating distinct aspects of cortical development...
  17. Wentzel P, Eriksson U. Altered gene expression in rat cranial neural crest cells exposed to a teratogenic glucose concentration in vitro: paradoxical downregulation of antioxidative defense genes. Birth Defects Res B Dev Reprod Toxicol. 2011;92:487-97 pubmed publisher
    ..These patterns of glucose-altered gene expression in a developmentally important cell population may be of etiological importance for NCC-associated malformations in diabetic pregnancy. ..
  18. Stober G, Syagailo Y, Okladnova O, Jungkunz G, Knapp M, Beckmann H, et al. Functional PAX-6 gene-linked polymorphic region: potential association with paranoid schizophrenia. Biol Psychiatry. 1999;45:1585-91 pubmed
    ..Our finding indicates that early developmental genes may be involved in the etiopathogenesis of schizophrenia subtypes via variable transcriptional regulation in the developing and adult human brain. ..
  19. Winner B, Desplats P, Hagl C, Klucken J, Aigner R, Ploetz S, et al. Dopamine receptor activation promotes adult neurogenesis in an acute Parkinson model. Exp Neurol. 2009;219:543-52 pubmed publisher vitro, and PPX specifically increased mRNA levels of epidermal growth factor receptor (EGF-R) and paired box gene 6 (Pax6)...
  20. Azuma N, Yamaguchi Y, Handa H, Hayakawa M, Kanai A, Yamada M. Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies. Am J Hum Genet. 1999;65:656-63 pubmed
    The PAX6 gene is involved in ocular morphogenesis, and PAX6 mutations have been detected in various types of ocular anomalies, including aniridia, Peters anomaly, corneal dystrophy, congenital cataract, and foveal hypoplasia...
  21. Hamasaki A, Yamada Y, Kurose T, Ban N, Nagashima K, Takahashi A, et al. Adult pancreatic islets require differential pax6 gene dosage. Biochem Biophys Res Commun. 2007;353:40-6 pubmed
    b>Pax6, a paired homeodomain transcription factor, plays crucial roles in morphogenesis of eye, central nervous system, and pancreatic islets...
  22. Xu Y, Chen C, Jin N, Zhu J, Kang L, Zhou T, et al. Müller glia cells activation in rat retina after optic nerve injury: spatiotemporal correlation with transcription initiation factor IIb. J Mol Neurosci. 2013;51:37-46 pubmed publisher
    ..In addition, we also examined the expression of the retinal progenitor markers (Nestin and Pax6) whose changes were correlated with the expression of TFIIB...
  23. Kim E, Noh Y, Ryu M, Kim H, Lee S, Kim C, et al. Phosphorylation and transactivation of Pax6 by homeodomain-interacting protein kinase 2. J Biol Chem. 2006;281:7489-97 pubmed
    b>Pax6 is a transcriptional activator that contains two DNA binding domains and a potent transcription activation domain in the C terminus, which regulates organogenesis of the eye, nose, pancreas, and central nervous system...
  24. Axton R, Hanson I, Danes S, Sellar G, van Heyningen V, Prosser J. The incidence of PAX6 mutation in patients with simple aniridia: an evaluation of mutation detection in 12 cases. J Med Genet. 1997;34:279-86 pubmed
    ..test what proportion of people with aniridia, uncomplicated by associated anomalies, carry mutations in the human PAX6 gene. Mutations were detected in 90% of the cases...
  25. Nomura T, Holmberg J, Frisen J, Osumi N. Pax6-dependent boundary defines alignment of migrating olfactory cortex neurons via the repulsive activity of ephrin A5. Development. 2006;133:1335-45 pubmed
    ..Here, we report Pax6-dependent alignment of the olfactory cortex neurons in the developing telencephalon...
  26. Takahashi M, Osumi N. Pax6 regulates boundary-cell specification in the rat hindbrain. Mech Dev. 2011;128:289-302 pubmed publisher
    ..In this study, we report that Pax6, a homeodomain transcription factor, regulates boundary-cell specification between rhombomeres of the developing ..
  27. Gosmain Y, Katz L, Masson M, Cheyssac C, Poisson C, Philippe J. Pax6 is crucial for ?-cell function, insulin biosynthesis, and glucose-induced insulin secretion. Mol Endocrinol. 2012;26:696-709 pubmed publisher
    The Pax6 transcription factor is crucial for endocrine cell differentiation and function. Indeed, mutations of Pax6 are associated with a diabetic phenotype and a drastic decrease of insulin-positive cell number...
  28. Jones K, Connor B. Proneural transcription factors Dlx2 and Pax6 are altered in adult SVZ neural precursor cells following striatal cell loss. Mol Cell Neurosci. 2011;47:53-60 pubmed publisher
    ..We therefore examined the expression of Mash1, Dlx2, Pax6 and Olig2 in SVZ-derived neural precursor cell populations across a range of times following quinolinic acid (QA) ..
  29. Makarenkova H, Ito M, Govindarajan V, Faber S, Sun L, McMahon G, et al. FGF10 is an inducer and Pax6 a competence factor for lacrimal gland development. Development. 2000;127:2563-72 pubmed
    ..Using a reporter transgene as a specific marker for gland epithelium, we show that the transcription factor Pax6 is required for normal development of the gland and is probably an important competence factor...
  30. Marakalala M, Vautier S, Potrykus J, Walker L, Shepardson K, Hopke A, et al. Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1. PLoS Pathog. 2013;9:e1003315 pubmed publisher
    ..albicans and the immune system and have significant implications for our understanding of susceptibility and treatment of human infections with this pathogen. ..
  31. Bishop K, Rubenstein J, O Leary D. Distinct actions of Emx1, Emx2, and Pax6 in regulating the specification of areas in the developing neocortex. J Neurosci. 2002;22:7627-38 pubmed
    ..The transcription factors EMX1, EMX2, and PAX6 have been proposed to regulate arealization...
  32. Lin Y, Liu X, Liang X, Li B, Jiang S, Ye S, et al. PAX6 analysis of one family and one sporadic patient from southern China with classic aniridia. Mol Vis. 2011;17:3116-20 pubmed
    To investigate the paired box gene 6 (PAX6) in three patients from southern China presenting with classic aniridia: two patients from two successive generations of one family and one sporadic patient.
  33. 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
    ..relationships analogous to those between ey, so, eya and dac exist in early mammalian oculogenesis, we investigated Pax6, Six3, Eya1 and Dach1 protein expression in murine lens and nasal placode development...
  34. Jin C, Wang Q, Li J, Zhu Y, Shentu X, Yao K. A recurrent PAX6 mutation is associated with aniridia and congenital progressive cataract in a Chinese family. Mol Vis. 2012;18:465-70 pubmed
    ..Aniridia is phenotyically and genetically heterogeneous. This study is to summarize the phenotypes and identify the genetic defect responsible for aniridia and congenital progressive cataract in a three generation Chinese family...
  35. Klempin F, Marr R, Peterson D. Modification of pax6 and olig2 expression in adult hippocampal neurogenesis selectively induces stem cell fate and alters both neuronal and glial populations. Stem Cells. 2012;30:500-9 pubmed publisher
    ..Using an in vivo retroviral delivery and lineage tracing approach, we compare the lineage-instruction factors, Pax6 and Olig2, and demonstrate that both participate in regulation of adult hippocampal neurogenesis in adult rats...
  36. Miyake M, Yamashiro K, Nakanishi H, Nakata I, Akagi Kurashige Y, Tsujikawa A, et al. Association of paired box 6 with high myopia in Japanese. Mol Vis. 2012;18:2726-35 pubmed
    The objective of this study was to investigate whether genetic variations in the paired box 6 (PAX6) gene are associated with high myopia in Japanese subjects...
  37. Tamai H, Shinohara H, Miyata T, Saito K, Nishizawa Y, Nomura T, et al. Pax6 transcription factor is required for the interkinetic nuclear movement of neuroepithelial cells. Genes Cells. 2007;12:983-96 pubmed
    ..b>Pax6 transcription factor plays pivotal roles in various aspects of corticogenesis...
  38. Ramaesh T, Ramaesh K, Martin Collinson J, Chanas S, Dhillon B, West J. Developmental and cellular factors underlying corneal epithelial dysgenesis in the Pax6+/- mouse model of aniridia. Exp Eye Res. 2005;81:224-35 pubmed
    Heterozygosity for a PAX6 deficiency (PAX6+/-) results in low levels of the PAX6 transcription factor and causes aniridia...
  39. Kredo Russo S, Mandelbaum A, Ness A, Alon I, Lennox K, Behlke M, et al. Pancreas-enriched miRNA refines endocrine cell differentiation. Development. 2012;139:3021-31 pubmed publisher
    ..We further demonstrate that Pax6 is an important target of miR-7...
  40. Chen P, Zang X, Sun D, Wang Y, Wang Y, Zhao X, et al. Mutation analysis of paired box 6 gene in inherited aniridia in northern China. Mol Vis. 2013;19:1169-77 pubmed
    ..This study is to summarize the phenotypes and identify the underlying genetic cause of the paired box 6 (PAX6) gene responsible for aniridia in two three-generation Chinese families in northern China.
  41. Skala Rubinson H, Vinh J, Labas V, Kahn A, Phan D. Novel target sequences for Pax-6 in the brain-specific activating regions of the rat aldolase C gene. J Biol Chem. 2002;277:47190-6 pubmed
    ..This result suggests that the brain-specific aldolase C gene could constitute a new target for the transcription factor Pax-6, which is implicated increasingly in neurogenesis. ..
  42. Grapp M, Teichler S, Kitz J, Dibaj P, Dickel C, Knepel W, et al. The homeodomain of PAX6 is essential for PAX6-dependent activation of the rat glucagon gene promoter: evidence for a PH0-like binding that induces an active conformation. Biochim Biophys Acta. 2009;1789:403-12 pubmed publisher
    The transcription factor PAX6 plays an important role in transcriptional regulation of the peptide hormone glucagon from pancreatic alpha-cells. PAX6 contains two DNA binding domains, the paired domain (PD) and the homeodomain (HD)...
  43. Wen J, Chen Y, Song S, Ding J, Gao Y, Hu Q, et al. Paired box 6 (PAX6) regulates glucose metabolism via proinsulin processing mediated by prohormone convertase 1/3 (PC1/3). Diabetologia. 2009;52:504-13 pubmed publisher
    Human patients with aniridia caused by heterozygous PAX6 mutations display abnormal glucose metabolism, but the underlying molecular mechanism is largely unknown...
  44. Grocott T, Frost V, Maillard M, Johansen T, Wheeler G, Dawes L, et al. The MH1 domain of Smad3 interacts with Pax6 and represses autoregulation of the Pax6 P1 promoter. Nucleic Acids Res. 2007;35:890-901 pubmed
    b>Pax6 transcription is under the control of two main promoters (P0 and P1), and these are autoregulated by Pax6...
  45. Yasuda T, Kajimoto Y, Fujitani Y, Watada H, Yamamoto S, Watarai T, et al. PAX6 mutation as a genetic factor common to aniridia and glucose intolerance. Diabetes. 2002;51:224-30 pubmed
    A paired homeodomain transcription factor, PAX6, is a well-known regulator of eye development, and its heterozygous mutations in humans cause congenital eye anomalies such as aniridia...
  46. Heller R, Stoffers D, Liu A, Schedl A, Crenshaw E, Madsen O, et al. The role of Brn4/Pou3f4 and Pax6 in forming the pancreatic glucagon cell identity. Dev Biol. 2004;268:123-34 pubmed
    Brain 4 (Brn4/Pou3f4) and Pax6 are POU-homeodomain and paired-homeodomain transcription factors, respectively, that are expressed in the brain and the glucagon-expressing cells in the pancreas...
  47. Mirzayans F, Pearce W, MacDonald I, Walter M. Mutation of the PAX6 gene in patients with autosomal dominant keratitis. Am J Hum Genet. 1995;57:539-48 pubmed
    ..Aniridia (shown recently to result from mutations in the PAX6 gene) has overlapping clinical findings and a similar pattern of inheritance with ADK...
  48. Tucker E, Segall S, Gopalakrishna D, Wu Y, Vernon M, Polleux F, et al. Molecular specification and patterning of progenitor cells in the lateral and medial ganglionic eminences. J Neurosci. 2008;28:9504-18 pubmed publisher
    ..Analyses of Pax6(Sey/Sey), Shh(-/-), and Gli3(XtJ/XtJ) mutants suggests that LGE and MGE progenitor identity does not rely ..
  49. Kim J, Lauderdale J. Analysis of Pax6 expression using a BAC transgene reveals the presence of a paired-less isoform of Pax6 in the eye and olfactory bulb. Dev Biol. 2006;292:486-505 pubmed
    b>Pax6, a member of the paired-family of transcription factors, exhibits restricted expression and essential functions in the developing eye, olfactory system, central nervous system, and pancreas...
  50. Grinchuk O, Kozmik Z, Wu X, Tomarev S. The Optimedin gene is a downstream target of Pax6. J Biol Chem. 2005;280:35228-37 pubmed
    ..The expression pattern of the Optimedin A variant in the eye and brain overlaps with that for Pax6, which encodes a protein containing the paired and homeobox DNA-binding domains...
  51. Nacher J, Varea E, Blasco Ibáñez J, Castillo Gomez E, Crespo C, Martinez Guijarro F, et al. Expression of the transcription factor Pax 6 in the adult rat dentate gyrus. J Neurosci Res. 2005;81:753-61 pubmed
    ..However, the expression of Pax 6 in astrocytes and certain mature neurons may indicate the existence of other roles for this transcription factor in this telencephalic region. ..
  52. Gil Sanz C, Landeira B, Ramos C, Costa M, M ller U. Proliferative defects and formation of a double cortex in mice lacking Mltt4 and Cdh2 in the dorsal telencephalon. J Neurosci. 2014;34:10475-87 pubmed publisher
    ..Our findings suggest that defects in adherens junctions components in mice massively affects progenitor cell proliferation and leads to a double cortex-like phenotype...
  53. Wu H, Liu Y, Wang H, Xu X. High-fat diet induced insulin resistance in pregnant rats through pancreatic pax6 signaling pathway. Int J Clin Exp Pathol. 2015;8:5196-202 pubmed
    ..RT-PCR and Real-time PCR were performed to study the expression of paired box 6 transcription factor (Pax6) and its target genes in pancreatic tissues...