Effects of aberrant Pax6 gene dosage on mouse corneal pathophysiology and corneal epithelial homeostasis

PLoS ONE

Volumn 6, Issue 12, 2011, Pages

  Mort, Richard L ^a,b   Bentley, Adam J ^c   Martin, Francis L ^d   Collinson, J Martin ^e   Douvaras, Panagiotis ^a   Hill, Robert E ^b   Morley, Steven D ^a   Fullwood, Nigel J ^c   West, John D ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

^c LANCASTER UNIVERSITY   (United Kingdom)

^d LANCASTER UNIVERSITY   (United Kingdom)

^e UNIVERSITY OF ABERDEEN   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BETA GALACTOSIDASE; TRANSCRIPTION FACTOR PAX6; TRANSCRIPTION FACTOR PAX7; EYE PROTEIN; HOMEODOMAIN PROTEIN; PAIRED BOX TRANSCRIPTION FACTOR; REPRESSOR PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANIRIDIA; ARTICLE; CELL VACUOLE; CHROMOSOME MOSAICISM; CONTROLLED STUDY; CORNEA EPITHELIUM; CORNEA STROMA; DISEASE SEVERITY; ELECTRON MICROSCOPY; GENE; GENE DOSAGE; GENE EXPRESSION; GENE OVEREXPRESSION; GENOTYPE; HETEROZYGOSITY; KERATOPATHY; LACZ GENE; MISSENSE MUTATION; MOUSE; NONHUMAN; PATHOPHYSIOLOGY; PAX6 GENE; PAX7 GENE; TRANSGENE; TRANSGENIC MOUSE; WILD TYPE; X CHROMOSOME INACTIVATION; ANIMAL; CELL JUNCTION; CONGENITAL MALFORMATION; ENDOTHELIUM CELL; FEMALE; GENETICS; HETEROZYGOTE; HOMEOSTASIS; HUMAN; MALE; METABOLISM; MICROVILLUS; MOSAICISM; PATHOLOGY; ULTRASTRUCTURE;

MUS;

ANIMALS; BETA-GALACTOSIDASE; CORNEAL STROMA; ENDOTHELIAL CELLS; EPITHELIUM, CORNEAL; EYE PROTEINS; FEMALE; GENE DOSAGE; GENOTYPE; HETEROZYGOTE; HOMEODOMAIN PROTEINS; HOMEOSTASIS; HUMANS; INTERCELLULAR JUNCTIONS; MALE; MICE; MICE, TRANSGENIC; MICROVILLI; MOSAICISM; PAIRED BOX TRANSCRIPTION FACTORS; REPRESSOR PROTEINS; TRANSGENES; X CHROMOSOME INACTIVATION;

EID: 84855267423     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0028895     Document Type: Article

References (66)

1. Hill RE, Favor J, Hogan BLM, Ton CCT, Saunders GF, et al. (1991) Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature 354: 522-525.
2. Halder G, Callaerts P, Gehring WJ, (1995) Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267: 1788-1792.
3. Quinn JC, West JD, Hill RE, (1996) Multiple functions for Pax6 in mouse eye and nasal development. Genes Dev 10: 435-446.
4. Ashery-Padan R, Marquardt T, Zhou XL, Gruss P, (2000) Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye. Genes Dev 14: 2701-2711.
5. Collinson JM, Hill RE, West JD, (2000) Different roles for Pax6 in the optic vesicle and facial epithelium mediate early morphogenesis of the murine eye. Development 127: 945-956.
6. Favor J, Gloeckner CJ, Neuhauser-Klaus A, Pretsch W, Sandulache R, et al. (2008) Relationship of Pax6 activity levels to the extent of eye development in the mouse, Mus musculus. Genetics 179: 1345-1355.
7. Aalfs CM, Fantes JA, Wenniger-Prick LJJM, Sluijter S, Hennekam RCM, et al. (1997) Tandem duplication of 11p12-p13 in a child with borderline development delay and eye abnormalities: Dose effect of the PAX6 gene product? Am J Med Genet 73: 267-271.
8. Schedl A, Ross A, Lee M, Engelkamp D, Rashbass P, et al. (1996) Influence of Pax6 gene dosage on development- overexpression causes severe eye abnormalities. Cell 86: 71-82.
9. Prosser J, van Heyningen V, (1998) PAX6 mutations reviewed. Hum Mut 11: 93-108.
10. Cotsarelis G, Cheng SZ, Dong G, Sun TT, Lavker RM, (1989) Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells. Cell 57: 201-209.
11. Beebe DC, Masters BR, (1996) Cell lineage and the differentiation of corneal epithelial cells. Invest Ophthalmol Vis Sci 37: 1815-1825.
12. Lehrer MS, Sun TT, Lavker RM, (1998) Strategies of epithelial repair: modulation of stem cell and transit amplifying cell proliferation. J Cell Sci 111: 2867-2875.
13. Li W, Hayashida Y, Chen YT, Tseng SCG, (2007) Niche regulation of corneal epithelial stem cells at the limbus. Cell Res 17: 26-36.
14. Secker GA, Daniels JT, (2009) Limbal epithelial stem cells of the cornea. StemBook: (ed. The Stem Cell Research Community, StemBook.) doi/10.3824/stembook.1.48.1,http://www.stembook.org.
15. Kruse FE, (1994) Stem cells and corneal epithelial regeneration. Eye 8: 170-183.
16. Ren HW, Wilson G, (1996) The cell shedding rate of the corneal epithelium- A comparison of collection methods. Curr Eye Res 15: 1054-1059.
17. Buck RC, (1985) Measurement of centripetal migration of normal corneal epithelial cells in the mouse. Invest Ophthalmol Vis Sci 26: 1296-1299.
18. Nagasaki T, Zhao J, (2003) Centripetal movement of corneal epithelial cells in the normal adult mouse. Invest Ophthalmol Vis Sci 44: 558-566.
19. Collinson JM, Morris L, Reid AI, Ramaesh T, Keighren MA, et al. (2002) Clonal analysis of patterns of growth, stem cell activity, and cell movement during the development and maintenance of the murine corneal epithelium. Dev Dyn 224: 432-440.
20. Collinson JM, Hill RE, West JD, (2004) Analysis of mouse eye development with chimeras and mosaics. Int J Dev Biol 48: 793-804.
21. Mort RL, Ramaesh T, Kleinjan DA, Morley SD, West JD, (2009) Mosaic analysis of stem cell function and wound healing in the mouse corneal epithelium. BMC Dev Biol 9: 4.
22. Endo M, Zoltick PW, Chung DC, Bennett J, Radu A, et al. (2007) Gene transfer to ocular stem cells by early gestational intraamniotic injection of lentiviral vector. Mol Therap 15: 579-587.
23. Grindley JC, Davidson DR, Hill RE, (1995) The role of Pax-6 in eye and nasal development. Development 121: 1433-1442.
24. Koroma BM, Yang JM, Sundin OH, (1997) The Pax-6 homeobox gene is expressed throughout the corneal and conjunctival epithelia. Invest Ophthalmol Vis Sci 38: 108-120.
25. Glaser T, Jepeal L, Edwards JG, Young SR, Favor J, et al. (1994) PAX6 gene dosage effects in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. Nat Genet 7: 463-471 (Correction, addition: Nat Genet 8: 203).
26. Ton CCT, Hirvonen H, Miwa H, Weil MM, Monaghan P, et al. (1991) Positional cloning and characterization of a paired box-containing and homeobox-containing gene from the aniridia region. Cell 67: 1059-1074.
27. Jordan T, Hanson I, Zaletayev D, Hodgson S, Prosser J, et al. (1992) The human PAX6 gene is mutated in two patients with aniridia. Nat Genet 1: 328-332.
28. Glaser T, Walton DS, Maas RL, (1992) Genomic structure, evolutionary conservation and aniridia mutations in the human Pax6 gene. Nature Genetics 2: 232-239.
29. Roberts RC, (1967) Small eyes- a new dominant eye mutant in the mouse. Genet Res 9: 121-122.
30. Hogan BLM, Hirst EMA, Horsburgh G, Hetherington CM, (1988) Small eye (Sey): a mouse model for the genetic analysis of craniofacial abnormalities. Development 103 (Suppl.): 115-119.
31. Favor J, Neuhauser-Klaus A, (2000) Saturation mutagenesis for dominant eye morphological defects in the mouse Mus musculus. Mamm Genome 11: 520-525.
32. St-Onge L, Sosa-Pineda B, Chowdhury K, Mansouri A, Gruss P, (1997) Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas. Nature 387: 406-409.
33. Hanson I, Churchill A, Love J, Axton R, Moore T, et al. (1999) Missense mutations in the most ancient residues of the PAX6 paired domain underlie a spectrum of human congenital eye malformations. Hum Mol Genet 8: 165-172.
34. Hever AM, Williamson KA, van Heyningen V, (2006) Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2. Clin Genet 69: 459-470.
35. van Heyningen V, Williamson KA, (2002) PAX6 in sensory development. Hum Mol Genet 11: 1161-1167.
36. Ramaesh T, Williams SE, Paul C, Ramaesh K, Dhillon B, et al. (2009) Histopathological characterisation of effects of the mouse Pax6Leca4 missense mutation on eye development. Exp Eye Res 89: 263-273.
37. Ramaesh T, Collinson JM, Ramaesh K, Kaufman MH, West JD, et al. (2003) Corneal abnormalities in Pax6+/- small eye mice mimic human aniridia-related keratopathy. Invest Ophthalmol Vis Sci 44: 1871-1878.
38. Davis J, Duncan MK, Robison WG, Piatigorsky J, (2003) Requirement for Pax6 in corneal morphogenesis: a role in adhesion. J Cell Sci 116: 2157-2167.
39. Ramaesh T, Ramaesh K, Collinson JM, Chanas SA, Dhillon B, et al. (2005) Developmental and cellular factors underlying corneal epithelial dysgenesis in the Pax6+/- mouse model of aniridia. Exp Eye Res 81: 224-235.
40. Ramaesh T, Ramaesh K, Leask R, Springbett A, Riley SC, et al. (2006) Increased apoptosis and abnormal wound-healing responses in the heterozygous Pax6+/- mouse cornea. Invest Ophthalmol Vis Sci 47: 1911-1917.
41. Kucerova R, Ou JX, Lawson D, Leiper LJ, Collinson JM, (2006) Cell surface glycoconjugate abnormalities and corneal epithelial wound healing in the Pax6+/- mouse model of aniridia-related keratopathy. Invest Ophthal Vis Sci 47: 5276-5282.
42. Leiper LJ, Walczysko P, Kucerova R, Ou JX, Shanley LJ, et al. (2006) The roles of calcium signaling and ERK1/2 phosphorylation in a Pax6+/- mouse model of epithelial wound-healing delay. BMC Biol 4.
43. Kanakubo S, Nomura T, Yamamura KI, Miyazaki JI, Tamai M, et al. (2006) Abnormal migration and distribution of neural crest cells in Pax6 heterozygous mutant eye, a model for human eye diseases. Genes Cells 11: 919-933.
44. Ou J, Walczysko P, Kucerova R, Rajnicek AM, McCaig CD, et al. (2008) Chronic wound state exacerbated by oxidative stress in Pax6+/- aniridia-related keratopathy. J Pathol 215: 421-430.
45. Leiper LJ, Ou JX, Walczysko P, Kucerova R, Lavery DN, et al. (2009) Control of patterns of corneal innervation by Pax6. Invest Ophthalmol Vis Sci 50: 1122-1128.
46. Ou JX, Lowes C, Collinson JM, (2010) Cytoskeletal and cell adhesion defects in wounded and Pax6+/- corneal pithelia. Invest Ophthalmol Vis Sci 51: 1415-1423.
47. Baulmann DC, Ohlmann A, Flugel-Koch C, Goswami S, Cvekl A, et al. (2002) Pax6 heterozygous eyes show defects in chamber angle differentiation that are associated with a wide spectrum of other anterior eye segment abnormalities. Mech Dev 118: 3-17.
48. Kroeber M, Davis N, Holzmann S, Kritzenberger M, Shelah-Goraly M, et al. (2010) Reduced expression of Pax6 in lens and cornea of mutant mice leads to failure of chamber angle development and juvenile glaucoma. Hum Mol Genet 19: 3332-3342.
49. Nishida K, Kinoshita S, Ohashi Y, Kuwayama Y, Yamamoto S, (1995) Ocular surface abnormalities in aniridia. Am J Ophthalmol 120: 368-375.
50. Holland EJ, Djalilian AR, Schwartz GS, (2003) Management of aniridic keratopathy with keratolimbal allograft: A limbal stem cell transplantation technique. Ophthalmology 110: 125-130.
51. Collinson JM, Chanas SA, Hill RE, West JD, (2004) Corneal development, limbal stem cell function, and corneal epithelial cell migration in the Pax6+/- mouse. Invest Ophthalmol Vis Sci 45: 1101-1108.
52. Manuel M, Georgala PA, Carr CB, Chanas S, Kleinjan DA, et al. (2007) Controlled overexpression of Pax6 in vivo negatively auto-regulates the Pax6 locus, causing cell-autonomous defects of late cortical progenitor proliferation with little effect on cortical arealization. Development 134: 545-555.
53. Manuel M, Pratt T, Liu M, Jeffery G, Price DJ, (2008) Overexpression of Pax6 results in microphthalmia, retinal dysplasia and defective retinal ganglion cell axon guidance. BMC Dev Biol 8.
54. Dorà N, Ou J, Kucerova R, Parisi I, West JD, et al. (2008) PAX6 dosage effects on corneal development, growth and wound healing. Dev Dyn 237: 1295-1306.
55. Chanas SA, Collinson JM, Ramaesh T, Dora N, Kleinjan DA, et al. (2009) Effects of elevated Pax6 expression and genetic background on mouse eye development. Invest Ophthalmol Vis Sci 50: 4045-4059.
56. Dorà N, (2009) The role of Pax6 in corneal development and maintenance. PhD thesis. University of Aberdeen.
57. Collinson JM, Quinn JC, Hill RE, West JD, (2003) The roles of Pax6 in the cornea, retina, and olfactory epithelium of the developing mouse embryo. Dev Biol 255: 303-312.
58. Snip RC, Kenyon KR, Green WR, (1973) Macular corneal dystrophy: Ultrastructural pathology of corneal endothelium and Descemet's membrane. Invest Ophthalmol 12: 88-97.
59. Lewis D, Davies Y, Nieduszynski IA, Lawrence F, Quantock AJ, et al. (2000) Ultrastructural localization of sulfated and unsulfated keratan sulfate in normal and macular corneal dystrophy type I. Glycobiology 10: 305-312.
60. Zhang W, Zhao J, Chen L, Urbanowicz MM, Nagasaki T, (2008) Abnormal epithelial homeostasis in the cornea of mice with a destrin deletion. Mol Vis 14: 1929-1939.
61. Nakagawa T, Nabeshima YI, Yoshida S, (2007) Functional identification of the actual and potential stem cell compartments in mouse spermatogenesis. Developmental Cell 12: 195-206.
62. Snippert HJ, van der Flier LG, Sato T, van Es JH, van den Born M, et al. (2010) Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 143: 134-144.
63. Lopez-Garcia C, Klein AM, Simons BD, Winton DJ, (2010) Intestinal stem cell replacement follows a pattern of neutral drift. Science 330: 822-825.
64. Puangsricharern V, Tseng SCG, (1995) Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology 102: 1476-1485.
65. Tan S-S, Williams EA, Tam PPL, (1993) X-chromosome inactivation occurs at different times in different tissues of the post-implantation mouse embryo. Nat Genet 3: 170-174.
66. Mort RL, (2009) Quantitative analysis of patch patterns in mosaic tissues with ClonalTools software. J Anat 215: 698-704.