About this Journal Submit a Manuscript Table of Contents
Journal of Ophthalmology
Volume 2013 (2013), Article ID 103947, 22 pages
http://dx.doi.org/10.1155/2013/103947
Review Article

Ocular Surface Development and Gene Expression

Departments of Ophthalmology, and Cell Biology and Physiology, McGowan Institute of Regenerative Medicine, University of Pittsburgh School of Medicine, 203 Lothrop Street, Room 1025, Pittsburgh, PA 15213, USA

Received 3 October 2012; Accepted 16 January 2013

Academic Editor: Terri L. Young

Copyright © 2013 Shivalingappa K. Swamynathan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. Pascolini and S. P. Mariotti, “Global estimates of visual impairment: 2010,” British Journal of Ophthalmology, vol. 96, pp. 614–618, 2012. View at Publisher · View at Google Scholar
  2. R. L. Chow and R. A. Lang, “Early eye development in vertebrates,” Annual Review of Cell and Developmental Biology, vol. 17, pp. 255–296, 2001. View at Publisher · View at Google Scholar · View at Scopus
  3. A. Cvekl and E. R. Tamm, “Anterior eye development and ocular mesenchyme: new insights from mouse models and human diseases,” BioEssays, vol. 26, no. 4, pp. 374–386, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. J. D. Zieske, “Corneal development associated with eyelid opening,” International Journal of Developmental Biology, vol. 48, no. 8-9, pp. 903–911, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. E. D. Hay, “Development of the vertebrate cornea,” International Review of Cytology, vol. 63, pp. 263–322, 1979.
  6. J. M. Collinson, L. Morris, A. I. Reid et al., “Clonal analysis of patterns of growth, stem cell activity, and cell movement during the development and maintenance of the murine corneal epithelium,” Developmental Dynamics, vol. 224, no. 4, pp. 432–440, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. G. Cotsarelis, S. Z. Cheng, G. Dong, T. T. Sun, and R. M. Lavker, “Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells,” Cell, vol. 57, no. 2, pp. 201–209, 1989. View at Scopus
  8. T. Nagasaki and J. Zha, “Centripetal movement of corneal epithelial cells in the normal adult mouse,” Investigative Ophthalmology and Visual Science, vol. 44, no. 2, pp. 558–566, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. J. Piatigorsky, “Gene sharing in lens and cornea: facts and implications,” Progress in Retinal and Eye Research, vol. 17, no. 2, pp. 145–174, 1998. View at Publisher · View at Google Scholar · View at Scopus
  10. J. V. Jester, T. Moller-Pedersen, J. Huang et al., “The cellular basis of corneal transparency: evidence for 'corneal crystallins',” Journal of Cell Science, vol. 112, Part 5, pp. 613–622, 1999. View at Scopus
  11. J. V. Jester, A. Budge, S. Fisher, and J. Huang, “Corneal keratocytes: phenotypic and species differences in abundant protein expression and in vitro light-scattering,” Investigative Ophthalmology and Visual Science, vol. 46, no. 7, pp. 2369–2378, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. N. Tanifuji-Terai, K. Terai, Y. Hayashi, T. I. Chikama, and W. W. Y. Kao, “Expression of keratin 12 and maturation of corneal epithelium during development and postnatal growth,” Investigative Ophthalmology and Visual Science, vol. 47, no. 2, pp. 545–551, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. H. P. Makarenkova, M. Ito, V. Govindarajan et al., “FGF10 is an inducer and Pax6 a competence factor for lacrimal gland development,” Development, vol. 127, no. 12, pp. 2563–2572, 2000. View at Scopus
  14. C. J. Nien, S. Massei, G. Lin et al., “The development of meibomian glands in mice,” Molecular Vision, vol. 16, pp. 1132–1140, 2010. View at Scopus
  15. V. Govindarajan, M. Ito, H. P. Makarenkova, R. A. Lang, and P. A. Overbeek, “Endogenous and ectopic gland induction by FGF-10,” Developmental Biology, vol. 225, no. 1, pp. 188–200, 2000. View at Publisher · View at Google Scholar · View at Scopus
  16. D. Gupta, S. A. K. Harvey, N. Kaminski, and S. K. Swamynathan, “Mouse conjunctival forniceal gene expression during postnatal development and its regulation by krüppel-like factor 4,” Investigative Ophthalmology and Visual Science, vol. 52, no. 8, pp. 4951–4962, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. W. Adachi, H. Ulanovsky, Y. Li, B. Norman, J. Davis, and J. Piatigorsky, “Serial analysis of gene expression (SAGE) in the rat limbal and central corneal epithelium,” Investigative Ophthalmology and Visual Science, vol. 47, no. 9, pp. 3801–3810, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. H. C. Turner, M. T. Budak, M. A. M. Akinci, and J. M. Wolosin, “Comparative analysis of human conjunctival and corneal epithelial gene expression with oligonucleotide microarrays,” Investigative Ophthalmology and Visual Science, vol. 48, no. 5, pp. 2050–2061, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. M. A. Akinci, H. Turner, M. Taveras et al., “Molecular profiling of conjunctival epithelial side- population stem cells: atypical cell surface markers and sources of a slow-cycling phenotype,” Investigative Ophthalmology and Visual Science, vol. 50, no. 9, pp. 4162–4172, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. M. A. Akinci, H. Turner, M. Taveras, and J. M. Wolosin, “Differential gene expression in the pig limbal side population: implications for stem cell cycling, replication, and survival,” Investigative Ophthalmology and Visual Science, vol. 50, no. 12, pp. 5630–5638, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Zhou, X. M. Li, and R. M. Lavker, “Transcriptional profiling of enriched populations of stem cells versus transient amplifying cells: a comparison of limbal and corneal epithelial basal cells,” Journal of Biological Chemistry, vol. 281, no. 28, pp. 19600–19609, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. A. M. Ozyildirim, G. J. Wistow, J. Gao et al., “The lacrimal gland transcriptome is an unusually rich source of rare and poorly characterized gene transcripts,” Investigative Ophthalmology and Visual Science, vol. 46, no. 5, pp. 1572–1580, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. J. L. Ubels, H. M. Hoffman, S. Srikanth, J. H. Resau, and C. P. Webb, “Gene expression in rat lacrimal gland duct cells collected using laser capture microdissection: evidence for K+secretion by duct cells,” Investigative Ophthalmology and Visual Science, vol. 47, no. 5, pp. 1876–1885, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. C. Q. Nguyen, A. Sharma, J. X. She, R. A. McIndoe, and A. B. Peck, “Differential gene expressions in the lacrimal gland during development and onset of keratoconjunctivitis sicca in Sjogren's syndrome (SJS)-like disease of the C57BL/6.NOD-Aec1Aec2 mouse,” Experimental Eye Research, vol. 88, no. 3, pp. 398–409, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. A. B. Peck, B. T. Saylor, L. Nguyen, et al., “Gene expression profiling of early-phase Sjogren's syndrome in C57BL/6.NOD-Aec1Aec2 mice identifies focal adhesion maturation associated with infiltrating leukocytes,” Investigative Ophthalmology & Visual Science, vol. 52, pp. 5647–5655, 2011. View at Publisher · View at Google Scholar
  26. J. L. Ubels, I. K. Gipson, S. J. Spurr-Michaud, A. S. Tisdale, R. E. Van Dyken, and M. P. Hatton, “Gene expression in human accessory lacrimal glands of wolfring,” Investigative Ophthalmology & Visual Science, vol. 53, no. 11, pp. 6738–6747, 2012.
  27. S. Liu, S. M. Richards, K. Lo, M. Hatton, A. Fay, and D. A. Sullivan, “Changes in gene expression in human meibomian gland dysfunction,” Investigative Ophthalmology and Visual Science, vol. 52, no. 5, pp. 2727–2740, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. T. Suzuki, F. Schirra, S. M. Richards, R. V. Jensen, and D. A. Sullivan, “Estrogen and progesterone control of gene expression in the mouse meibomian gland,” Investigative Ophthalmology and Visual Science, vol. 49, no. 5, pp. 1797–1808, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. D. A. Sullivan, R. V. Jensen, T. Suzuki, and S. M. Richards, “Do sex steroids exert sex-specific and/or opposite effects on gene expression in lacrimal and meibomian glands?” Molecular Vision, vol. 15, pp. 1553–1572, 2009. View at Scopus
  30. F. Wu, S. Lee, M. Schumacher, A. Jun, and S. Chakravarti, “Differential gene expression patterns of the developing and adult mouse cornea compared to the lens and tendon,” Experimental Eye Research, vol. 87, no. 3, pp. 214–225, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. B. Norman, J. Davis, and J. Piatigorsky, “Postnatal gene expression in the normal mouse cornea by SAGE,” Investigative Ophthalmology and Visual Science, vol. 45, no. 2, pp. 429–440, 2004. View at Publisher · View at Google Scholar · View at Scopus
  32. D. Kenchegowda, S. A. K. Harvey, S. Swamynathan, K. L. Lathrop, and S. K. Swamynathan, “Critical role of Klf5 in regulating gene expression during post-eyelid opening maturation of mouse corneas,” PLoS One, vol. 7, article e44771, 2012.
  33. R. E. Hausman, “Ocular extracellular matrices in development,” Progress in Retinal and Eye Research, vol. 26, no. 2, pp. 162–188, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. J. M. Sivak and M. E. Fini, “MMPs in the eye: emerging roles for matrix metalloproteinases in ocular physiology,” Progress in Retinal and Eye Research, vol. 21, no. 1, pp. 1–14, 2002. View at Publisher · View at Google Scholar · View at Scopus
  35. J. M. Wolosin, M. T. Budak, and M. A. M. Akinci, “Ocular surface epithelial and stem cell development,” International Journal of Developmental Biology, vol. 48, no. 8-9, pp. 981–991, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. M. E. Fini and B. M. Stramer, “How the cornea heals: cornea-specific repair mechanisms affecting surgical outcomes,” Cornea, vol. 24, no. 8, pp. S2–S11, 2005. View at Scopus
  37. F. Majo, A. Rochat, M. Nicolas, G. A. Jaoudé, and Y. Barrandon, “Oligopotent stem cells are distributed throughout the mammalian ocular surface,” Nature, vol. 456, no. 7219, pp. 250–254, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. S. Burman and V. Sangwan, “Cultivated limbal stem cell transplantation for ocular surface reconstruction,” Journal of Clinical Ophthalmology, vol. 2, pp. 489–502, 2008.
  39. M. Fernandes, V. S. Sangwan, S. K. Rao et al., “Limbal Stem Cell Transplantation,” Indian Journal of Ophthalmology, vol. 52, no. 1, pp. 5–22, 2004. View at Scopus
  40. V. S. Sangwan, S. Basu, S. MacNeil, and D. Balasubramanian, “Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency,” British Journal of Ophthalmology, vol. 96, pp. 931–934, 2012. View at Publisher · View at Google Scholar
  41. V. S. Sangwan, G. K. Vemuganti, S. Singh, and D. Balasubramanian, “Successful reconstruction of damaged ocular outer surface in humans using limbal and conjuctival stem cell culture methods,” Bioscience Reports, vol. 23, no. 4, pp. 169–174, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. G. K. Vemuganti, V. S. Sangwan, and G. N. Rao, “The promise of stem cell therapy for eye disorders: guest Editorial,” Clinical and Experimental Optometry, vol. 90, no. 5, pp. 315–316, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. P. Rama, S. Matuska, G. Paganoni, A. Spinelli, M. De Luca, and G. Pellegrini, “Limbal stem-cell therapy and long-term corneal regeneration,” The New England Journal of Medicine, vol. 363, no. 2, pp. 147–155, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. B. B. Kulkarni, P. J. Tighe, I. Mohammed et al., “Comparative transcriptional profiling of the limbal epithelial crypt demonstrates its putative stem cell niche characteristics,” BMC Genomics, vol. 11, no. 1, article 526, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. V. Barbaro, A. Testa, E. Di Iorio, F. Mavilio, G. Pellegrini, and M. De Luca, “C/EBPδ regulates cell cycle and self-renewal of human limbal stem cells,” Journal of Cell Biology, vol. 177, no. 6, pp. 1037–1049, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. E. C. Figueira, N. Di Girolamo, M. T. Coroneo, and D. Wakefield, “The phenotype of limbal epithelial stem cells,” Investigative Ophthalmology and Visual Science, vol. 48, no. 1, pp. 144–156, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. R. Hayashi, M. Yamato, H. Sugiyama et al., “N-cadherin is expressed by putative stem/progenitor cells and melanocytes in the human limbal epithelial stem cell niche,” Stem Cells, vol. 25, no. 2, pp. 289–296, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. H. Qi, D. Q. Li, H. D. Shine et al., “Nerve growth factor and its receptor TrkA serve as potential markers for human corneal epithelial progenitor cells,” Experimental Eye Research, vol. 86, no. 1, pp. 34–40, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. P. B. Thomas, Y. H. Liu, F. F. Zhuang et al., “Identification of Notch-1 expression in the limbal basal epithelium,” Molecular Vision, vol. 13, pp. 337–344, 2007. View at Scopus
  50. L. Takács, E. Tóth, G. Losonczy et al., “Differentially expressed genes associated with human limbal epithelial phenotypes: new molecules that potentially facilitate selection of stem cell-enriched populations,” Investigative Ophthalmology and Visual Science, vol. 52, no. 3, pp. 1252–1260, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. M. Lyngholm, P. E. Høyer, H. Vorum, K. Nielsen, N. Ehlers, and K. Møllgård, “Immunohistochemical markers for corneal stem cells in the early developing human eye,” Experimental Eye Research, vol. 87, no. 2, pp. 115–121, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Lyngholm, H. Vorum, K. Nielsen, M. Ostergaard, B. Honoré, and N. Ehlers, “Differences in the protein expression in limbal versus central human corneal epithelium—a search for stem cell markers,” Experimental Eye Research, vol. 87, no. 2, pp. 96–105, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. M. N. Nakatsu, Z. Ding, M. Y. Ng, T. T. Truong, F. Yu, and S. X. Deng, “Wnt/beta-catenin signaling regulates proliferation of human cornea epithelial stem/progenitor cells,” Investigative Ophthalmology & Visual Science, vol. 52, pp. 4734–4741, 2011. View at Publisher · View at Google Scholar
  54. Y. J. Hsueh, P. C. Kuo, and J. K. Chen, “Transcriptional regulators of the DeltaNp63: their role in limbal epithelial cell proliferation,” Journal of Cellular Physiologyl, vol. 228, no. 3, pp. 536–546, 2013. View at Publisher · View at Google Scholar
  55. R. Lu, Y. Qu, J. Ge, et al., “Transcription factor TCF4 maintains the properties of human corneal epithelial stem cells,” Stem Cells, vol. 30, pp. 753–761, 2012. View at Publisher · View at Google Scholar
  56. R. A. Thoft, “The role of the limbus in ocular surface maintenance and repair,” Acta Ophthalmologica, vol. 67, no. 192, pp. 91–94, 1989. View at Scopus
  57. R. A. Thoft, L. A. Wiley, and N. Sundarraj, “The multipotential cells of the limbus,” Eye, vol. 3, Part 2, pp. 109–113, 1989. View at Scopus
  58. I. K. Gipson, “The ocular surface: the challenge to enable and protect vision. The Friedenwald lecture,” Investigative Ophthalmology & Visual Science, vol. 48, no. 10, pp. 4391–4398, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. H. Wan, K. H. Kaestner, S. L. Ang et al., “Foxa2 regulates alveolarization and goblet cell hyperplasia,” Development, vol. 131, no. 4, pp. 953–964, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. D. Z. Ye and K. H. Kaestner, “Foxa1 and Foxa2 Control the Differentiation of Goblet and Enteroendocrine L- and D-Cells in Mice,” Gastroenterology, vol. 137, no. 6, pp. 2052–2062, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. K. S. Park, T. R. Korfhagen, M. D. Bruno et al., “SPDEF regulates goblet cell hyperplasia in the airway epithelium,” Journal of Clinical Investigation, vol. 117, no. 4, pp. 978–988, 2007. View at Publisher · View at Google Scholar · View at Scopus
  62. G. Chen, T. R. Korfhagen, Y. Xu et al., “SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production,” Journal of Clinical Investigation, vol. 119, no. 10, pp. 2914–2924, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. A. Gregorieff, D. E. Stange, P. Kujala et al., “The ets-domain transcription factor spdef promotes maturation of goblet and paneth cells in the intestinal epithelium,” Gastroenterology, vol. 137, no. 4, pp. 1333–1345, 2009. View at Publisher · View at Google Scholar · View at Scopus
  64. D. Kenchegowda, S. Swamynathan, D. Gupta, H. Wan, J. Whitsett a, and S. K. Swamynathan, “Conditional disruption of mouse Klf5 results in defective eyelids with malformed meibomian glands, abnormal cornea and loss of conjunctival goblet cells,” Developmental Biology, vol. 356, no. 1, pp. 5–18, 2011.
  65. S. K. Swamynathan, J. P. Katz, K. H. Kaestner, R. Ashery-Padan, M. A. Crawford, and J. Piatigorsky, “Conditional deletion of the mouse Klf4 gene results in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells,” Molecular and Cellular Biology, vol. 27, no. 1, pp. 182–194, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. S. K. Swamynathan, J. Davis, and J. Piatigorsky, “Identification of candidate Klf4 target genes reveals the molecular basis of the diverse regulatory roles of Klf4 in the mouse cornea,” Investigative Ophthalmology and Visual Science, vol. 49, no. 8, pp. 3360–3370, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. T. K. Noah, A. Kazanjian, J. Whitsett, and N. F. Shroyer, “SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells,” Experimental Cell Research, vol. 316, no. 3, pp. 452–465, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. W. P. Kloosterman and R. H. A. Plasterk, “The diverse functions of microRNAs in animal development and disease,” Developmental Cell, vol. 11, no. 4, pp. 441–450, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. D. G. Ryan, M. Oliveira-Fernandes, and R. M. Lavker, “MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity,” Molecular Vision, vol. 12, pp. 1175–1184, 2006. View at Scopus
  70. M. Karali, I. Peluso, V. A. Gennarino et al., “MiRNeye: a microRNA expression atlas of the mouse eye,” BMC Genomics, vol. 11, no. 1, article 715, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. M. Karali, I. Peluso, V. Marigo, and S. Banfi, “Identification and characterization of micrornas expressed in the mouse eye,” Investigative Ophthalmology & Visual Science, vol. 48, no. 2, pp. 509–515, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. Y. Li and J. Piatigorsky, “Targeted deletion of dicer disrupts lens morphogenesis, corneal epithelium stratification, and whole eye development,” Developmental Dynamics, vol. 238, no. 9, pp. 2388–2400, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. A. E. Hughes, D. T. Bradley, M. Campbell, et al., “Mutation altering the miR-184 seed region causes familial keratoconus with cataract,” The American Journal of Human Genetics, vol. 89, pp. 628–633, 2011.
  74. R. Shalom-Feuerstein, L. Serror, S. F. Divonne, et al., “Pluripotent stem cell model reveals essential roles for miR-450b-5p and miR-184 in embryonic corneal lineage specification,” Stem Cells, vol. 30, pp. 898–909, 2012. View at Publisher · View at Google Scholar
  75. J. Yu, D. G. Ryan, S. Getsios, M. Oliveira-Fernandes, A. Fatima, and R. M. Lavker, “MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 49, pp. 19300–19305, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. S. K. W. Lee, Y. Teng, H. K. Wong et al., “MicroRNA-145 regulates human corneal epithelial differentiation,” PLoS ONE, vol. 6, no. 6, article e21249, Article ID e21249, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. W. J. Gehring, “Historical perspective on the development and evolution of eyes and photoreceptors,” International Journal of Developmental Biology, vol. 48, no. 8-9, pp. 707–717, 2004. View at Publisher · View at Google Scholar · View at Scopus
  78. X. Zhang, A. Friedman, S. Heaney, P. Purcell, and R. L. Maas, “Meis homeoproteins directly regulate Pax6 during vertebrate lens morphogenesis,” Genes and Development, vol. 16, no. 16, pp. 2097–2107, 2002. View at Publisher · View at Google Scholar · View at Scopus
  79. R. Ashery-Padan, T. Marquardt, X. Zhou, and P. Gruss, “Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye,” Genes and Development, vol. 14, no. 21, pp. 2701–2711, 2000. View at Publisher · View at Google Scholar · View at Scopus
  80. B. M. Koroma, J. M. Yang, and O. H. Sundin, “The Pax-6 homeobox gene is expressed throughout the corneal and conjunctival epithelia,” Investigative Ophthalmology & Visual Science, vol. 38, no. 1, pp. 108–120, 1997. View at Scopus
  81. T. I. Simpson and D. J. Price, “Pax6; a pleiotropic player in development,” BioEssays, vol. 24, no. 11, pp. 1041–1051, 2002. View at Publisher · View at Google Scholar · View at Scopus
  82. J. M. Collinson, J. C. Quinn, R. E. Hill, and J. D. West, “The roles of Pax6 in the cornea, retina, and olfactory epithelium of the developing mouse embryo,” Developmental Biology, vol. 255, no. 2, pp. 303–312, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. J. Davis, M. K. Duncan, W. G. Robison Jr., and J. Piatigorsky, “Requirement for Pax6 in corneal morphogenesis: a role in adhesion,” Journal of Cell Science, vol. 116, no. 11, pp. 2157–2167, 2003. View at Publisher · View at Google Scholar · View at Scopus
  84. L. J. Leiper, J. Ou, P. Walczysko, et al., “Control of patterns of corneal innervation by Pax6,” Investigative Ophthalmology & Visual Science, vol. 50, pp. 1122–1128, 2009.
  85. J. Graw, “The genetic and molecular basis of congenital eye defects,” Nature Reviews Genetics, vol. 4, no. 11, pp. 876–888, 2003. View at Publisher · View at Google Scholar · View at Scopus
  86. I. M. Hanson, J. M. Fletcher, T. Jordan et al., “Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peter's anomaly,” Nature Genetics, vol. 6, no. 2, pp. 168–173, 1994. View at Publisher · View at Google Scholar · View at Scopus
  87. T. Jordan, I. Hanson, D. Zaletayev et al., “The human PAX6 gene is mutated in two patients with aniridia,” Nature Genetics, vol. 1, no. 5, pp. 328–332, 1992. View at Scopus
  88. I. M. Hanson, “PAX6 and Congenital Eye Malformations,” Pediatric Research, vol. 54, no. 6, pp. 791–796, 2003. View at Publisher · View at Google Scholar · View at Scopus
  89. B. L. M. Hogan, E. M. A. Hirst, G. Horsburgh, and C. M. Hetherington, “Small eye (Sey): a mouse model for the genetic analysis of craniofacial abnormalities,” Development, vol. 103, pp. 115–119, 1988. View at Scopus
  90. T. Ramaesh, J. M. Collinson, K. Ramaesh, M. H. Kaufman, J. D. West, and B. Dhillon, “Corneal abnormalities in Pax6+/- small eye mice mimic human aniridia-related keratopathy,” Investigative Ophthalmology and Visual Science, vol. 44, no. 5, pp. 1871–1878, 2003. View at Publisher · View at Google Scholar · View at Scopus
  91. J. M. Collinson, J. C. Quinn, M. A. Buchanan et al., “Primary defects in the lens underlie complex anterior segment abnormalities of the Pax6 heterozygous eye,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 17, pp. 9688–9693, 2001. View at Publisher · View at Google Scholar · View at Scopus
  92. R. Kucerova, J. Ou, D. Lawson, L. J. Leiper, and J. M. Collinson, “Cell surface glycoconjugate abnormalities and corneal epithelial wound healing in the Pax6+/- mouse model of aniridia-related keratopathy,” Investigative Ophthalmology & Visual Science, vol. 47, no. 12, pp. 5276–5282, 2006. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Kanakubo, T. Nomura, K. I. Yamamura, J. I. Miyazaki, M. Tamai, and N. Osumi, “Abnormal migration and distribution of neural crest cells in Pax6 heterozygous mutant eye, a model for human eye diseases,” Genes to Cells, vol. 11, no. 8, pp. 919–933, 2006. View at Publisher · View at Google Scholar · View at Scopus
  94. N. Dorà, J. Ou, R. Kucerova, I. Parisi, J. D. West, and J. M. Collinson, “PAX6 dosage effects on corneal development, growth, and wound healing,” Developmental Dynamics, vol. 237, no. 5, pp. 1295–1306, 2008. View at Publisher · View at Google Scholar · View at Scopus
  95. J. Davis and J. Piatigorsky, “Overexpression of Pax6 in mouse cornea directly alters corneal epithelial cells: changes in immune functionvascularization, and differentiation,” Investigative Ophthalmology & Visual Science, vol. 52, pp. 4158–4168, 2011. View at Publisher · View at Google Scholar
  96. J. Ouyang, Y. C. Shen, L. K. Yeh et al., “Pax6 overexpression suppresses cell proliferation and retards the cell cycle in corneal epithelial cells,” Investigative Ophthalmology & Visual Science, vol. 47, no. 6, pp. 2397–2407, 2006. View at Publisher · View at Google Scholar · View at Scopus
  97. R. Kucerova, N. Dora, R. L. Mort, et al., “Interaction between hedgehog signalling and PAX6 dosage mediates maintenance and regeneration of the corneal epithelium,” Molecular Vision, vol. 18, pp. 139–150, 2012.
  98. R. L. Mort, A. J. Bentley, F. L. Martin, et al., “Effects of aberrant Pax6 gene dosage on mouse corneal pathophysiology and corneal epithelial homeostasis,” PLoS One, vol. 6, article e28895, 2011.
  99. S. I. Aota, N. Nakajima, R. Sakamoto, S. Watanabe, N. Ibaraki, and K. Okazaki, “Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene,” Developmental Biology, vol. 257, no. 1, pp. 1–13, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. I. Brownell, M. Dirksen, and M. Jamrich, “Forkhead Foxe3 maps to the dysgenetic lens locus and is critical in lens development and differentiation,” Genesis, vol. 27, pp. 81–93, 2000.
  101. B. K. Chauhan, N. A. Reed, Y. Yang et al., “A comparative cDNA microarray analysis reveals a spectrum of genes regulated by Pax6 in mouse lens,” Genes to Cells, vol. 7, no. 12, pp. 1267–1283, 2002. View at Publisher · View at Google Scholar · View at Scopus
  102. A. Cvekl, Y. Yang, B. K. Chauhan, and K. Cveklova, “Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens,” International Journal of Developmental Biology, vol. 48, no. 8-9, pp. 829–844, 2004. View at Publisher · View at Google Scholar · View at Scopus
  103. M. K. Duncan, A. Cvekl, X. Li, and J. Piatigorsky, “Truncated forms of Pax-6 disrupt lens morphology in transgenic mice,” Investigative Ophthalmology & Visual Science, vol. 41, no. 2, pp. 464–473, 2000. View at Scopus
  104. Y. Furuta and B. L. M. Hogan, “BMP4 is essential for lens induction in the mouse embryo,” Genes and Development, vol. 12, no. 23, pp. 3764–3775, 1998. View at Scopus
  105. T. Marquardt, R. Ashery-Padan, N. Andrejewski, R. Scardigli, F. Guillemot, and P. Gruss, “Pax6 is required for the multipotent state of retinal progenitor cells,” Cell, vol. 105, no. 1, pp. 43–55, 2001. View at Publisher · View at Google Scholar · View at Scopus
  106. P. A. Zaki, J. M. Collinson, J. Toraiwa, T. I. Simpson, D. J. Price, and J. C. Quinn, “Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced by heterozygous mutation of Pax6,” BMC Developmental Biology, vol. 6, article 46, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. W. Liu, O. V. Lagutin, M. Mende, A. Streit, and G. Oliver, “Six3 activation of Pax6 expression is essential for mammalian lens induction and specification,” EMBO Journal, vol. 25, no. 22, pp. 5383–5395, 2006. View at Publisher · View at Google Scholar · View at Scopus
  108. O. Lagutin, C. C. Zhu, Y. Furuta, D. H. Rowitch, A. P. McMahon, and G. Oliver, “Six3 promotes the formation of ectopic optic vesicle-like structures in mouse embryos,” Developmental Dynamics, vol. 221, no. 3, pp. 342–349, 2001. View at Publisher · View at Google Scholar · View at Scopus
  109. G. Oliver, A. Mailhos, R. Wehr, N. G. Copeland, N. A. Jenkins, and P. Gruss, “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,” Development, vol. 121, no. 12, pp. 4045–4055, 1995. View at Scopus
  110. G. Goudreau, P. Petrou, L. W. Reneker, J. Graw, J. Löster, and P. Gruss, “Mutually regulated expression of Pax6 and Six3 and its implications for the Pax6 haploinsufficient lens phenotype,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 13, pp. 8719–8724, 2002. View at Publisher · View at Google Scholar · View at Scopus
  111. G. A. Secker and J. T. Daniels, “Corneal epithelial stem cells: deficiency and regulation,” Stem Cell Reviews, vol. 4, no. 3, pp. 159–168, 2008. View at Publisher · View at Google Scholar · View at Scopus
  112. W. Li, Y. T. Chen, Y. Hayashida et al., “Down-regulation of Pax6 is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases,” Journal of Pathology, vol. 214, no. 1, pp. 114–122, 2008. View at Publisher · View at Google Scholar · View at Scopus
  113. T. Ramaesh, K. Ramaesh, J. M. Collinson, S. A. Chanas, B. Dhillon, and J. D. West, “Developmental and cellular factors underlying corneal epithelial dysgenesis in the Pax6+/- mouse model of aniridia,” Experimental Eye Research, vol. 81, no. 2, pp. 224–235, 2005. View at Publisher · View at Google Scholar · View at Scopus
  114. J. M. Sivak, J. A. West-Mays, A. Yee, T. Williams, and M. E. Fini, “Transcription factors Pax6 and AP-2α interact to coordinate corneal epithelial repair by controlling expression of matrix metalloproteinase gelatinase B,” Molecular and Cellular Biology, vol. 24, no. 1, pp. 245–257, 2004. View at Publisher · View at Google Scholar · View at Scopus
  115. J. M. Sivak, R. Mohan, W. B. Rinehart, P. X. Xu, R. L. Maas, and M. E. Fini, “Pax-6 expression and activity are induced in the reepithelializing cornea and control activity of the transcriptional promoter for matrix metalloproteinase gelatinase B,” Developmental Biology, vol. 222, no. 1, pp. 41–54, 2000. View at Publisher · View at Google Scholar · View at Scopus
  116. A. L. Evans and P. J. Gage, “Expression of the homeobox gene Pitx2 in neural crest is required for optic stalk and ocular anterior segment development,” Human Molecular Genetics, vol. 14, no. 22, pp. 3347–3359, 2005. View at Publisher · View at Google Scholar · View at Scopus
  117. M. Asai-Coakwell, C. Backhouse, R. J. Casey, P. J. Gage, and O. J. Lehmann, “Reduced human and murine corneal thickness in an Axenfeld-Rieger syndrome subtype,” Investigative Ophthalmology & Visual Science, vol. 47, no. 11, pp. 4905–4909, 2006. View at Publisher · View at Google Scholar · View at Scopus
  118. J. Holmberg, C. Y. Liu, and T. A. Hjalt, “PITX2 gain-of-function in Rieger syndrome eye model,” American Journal of Pathology, vol. 165, no. 5, pp. 1633–1641, 2004. View at Scopus
  119. P. J. Gage, M. Qian, D. Wu, and K. I. Rosenberg, “The canonical Wnt signaling antagonist DKK2 is an essential effector of PITX2 function during normal eye development,” Developmental Biology, vol. 317, no. 1, pp. 310–324, 2008. View at Publisher · View at Google Scholar · View at Scopus
  120. S. Kumar and G. Duester, “Retinoic acid signaling in perioptic mesenchyme represses Wnt signaling via induction of Pitx2 and Dkk2,” Developmental Biology, vol. 340, no. 1, pp. 67–74, 2010. View at Publisher · View at Google Scholar · View at Scopus
  121. J. Weng, J. Luo, X. Cheng et al., “Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 16, pp. 6081–6086, 2008. View at Publisher · View at Google Scholar · View at Scopus
  122. M. M. Lucey, Y. Wang, M. Bustin, and M. K. Duncan, “Differential expression of the HMGN family of chromatin proteins during ocular development,” Gene Expression Patterns, vol. 8, no. 6, pp. 433–437, 2008. View at Publisher · View at Google Scholar · View at Scopus
  123. Y. Birger, J. Davis, T. Furusawa, E. Rand, J. Piatigorsky, and M. Bustin, “A role for chromosomal protein HMGN1 in corneal maturation,” Differentiation, vol. 74, no. 1, pp. 19–29, 2006. View at Publisher · View at Google Scholar · View at Scopus
  124. D. Weigel and H. Jackle, “The fork head domain: a novel DNA binding motif of eukaryotic transcription factors?” Cell, vol. 63, no. 3, pp. 455–456, 1990. View at Publisher · View at Google Scholar · View at Scopus
  125. G. Tuteja and K. H. Kaestner, “SnapShot: forkhead transcription factors II,” Cell, vol. 131, no. 1, p. 192, 2007. View at Publisher · View at Google Scholar · View at Scopus
  126. G. Tuteja and K. H. Kaestner, “SnapShot: forkhead transcription factors I,” Cell, vol. 130, no. 6, p. 1160, 2007. View at Publisher · View at Google Scholar · View at Scopus
  127. K. H. Kaestner, W. Knöchel, and D. E. Martínez, “Unified nomenclature for the winged helix/forkhead transcription factors,” Genes and Development, vol. 14, no. 2, pp. 142–146, 2000. View at Scopus
  128. O. J. Lehmann, J. C. Sowden, P. Carlsson, T. Jordan, and S. S. Bhattacharya, “Fox's in development and disease,” Trends in Genetics, vol. 19, no. 6, pp. 339–344, 2003. View at Publisher · View at Google Scholar · View at Scopus
  129. A. Blixt, H. Landgren, B. R. Johansson, and P. Carlsson, “Foxe3 is required for morphogenesis and differentiation of the anterior segment of the eye and is sensitive to Pax6 gene dosage,” Developmental Biology, vol. 302, no. 1, pp. 218–229, 2007. View at Publisher · View at Google Scholar · View at Scopus
  130. H. Hiemisch, G. Schütz, and K. H. Kaestner, “The mouse Fkh1/Mf1 gene: cDNA sequence, chromosomal localization and expression in adult tissues,” Gene, vol. 220, no. 1-2, pp. 77–82, 1998. View at Publisher · View at Google Scholar · View at Scopus
  131. H. K. Hong, J. H. Lass, and A. Chakravarti, “Pleiotropic skeletal and ocular phenotypes of the mouse mutation congenital hydrocephalus (ch/Mf1) arise from a winged helix/forkhead transcription factor gene,” Human Molecular Genetics, vol. 8, no. 4, pp. 625–637, 1999. View at Scopus
  132. R. A. Honkanen, D. Y. Nishimura, R. E. Swiderski et al., “A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene,” American Journal of Ophthalmology, vol. 135, no. 3, pp. 368–375, 2003. View at Publisher · View at Google Scholar · View at Scopus
  133. S. H. Kidson, T. Kume, K. Deng, V. Winfrey, and B. L. M. Hogan, “The forkhead/winged-helix gene, Mf1, is necessary for the normal development of the cornea and formation of the anterior chamber in the mouse eye,” Developmental Biology, vol. 211, no. 2, pp. 306–322, 1999. View at Publisher · View at Google Scholar · View at Scopus
  134. O. Lehmann, S. Tuft, G. Brice et al., “Novel anterior segment phenotypes resulting from forkhead gene alterations: evidence for cross-species conservation of function,” Investigative Ophthalmology & Visual Science, vol. 44, no. 6, pp. 2627–2633, 2003. View at Publisher · View at Google Scholar · View at Scopus
  135. D. Mattiske, P. Sommer, S. H. Kidson, and B. L. M. Hogan, “The role of the forkhead transcription factor, Foxc1, in the development of the mouse lacrimal gland,” Developmental Dynamics, vol. 235, no. 4, pp. 1074–1080, 2006. View at Publisher · View at Google Scholar · View at Scopus
  136. R. McKeone, H. Vieira, K. Gregory-Evans, C. Y. Gregory-Evans, and P. Denny, “Foxf2: a novel locus for anterior segment dysgenesis adjacent to the Foxc1 gene,” PLoS One, vol. 6, article e25489, 2011.
  137. M. Ormestad, A. Blixt, A. Churchill, T. Martinsson, S. Enerbäck, and P. Carlsson, “Foxe3 haploinsufficiency in mice: a model for Peters' anomaly,” Investigative Ophthalmology & Visual Science, vol. 43, no. 5, pp. 1350–1357, 2002. View at Scopus
  138. S. Seo, H. P. Singh, P. M. Lacal, et al., “Forkhead box transcription factor FoxC1 preserves corneal transparency by regulating vascular growth,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, pp. 2015–2020, 2012. View at Publisher · View at Google Scholar
  139. R. S. Smith, A. Zabaleta, T. Kume et al., “Haploinsufficiency of the transcription factors FOXC1 and FOXC2 results in aberrant ocular development,” Human Molecular Genetics, vol. 9, no. 7, pp. 1021–1032, 2000. View at Scopus
  140. J. Zhao, K. Kawai, H. Wang, et al., “Loss of Msx2 function down-regulates the FoxE3 expression and results in anterior segment dysgenesis resembling Peters anomaly,” American Journal of Pathology, vol. 180, pp. 2230–2239, 2012. View at Publisher · View at Google Scholar
  141. T. Kume, K. Y. Deng, V. Winfrey, D. B. Gould, M. A. Walter, and B. L. M. Hogan, “The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation congenital hydrocephalus,” Cell, vol. 93, no. 6, pp. 985–996, 1998. View at Publisher · View at Google Scholar · View at Scopus
  142. A. J. Mears, T. Jordan, F. Mirzayans et al., “Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly,” American Journal of Human Genetics, vol. 63, no. 5, pp. 1316–1328, 1998. View at Publisher · View at Google Scholar · View at Scopus
  143. F. Mirzayans, D. B. Gould, E. Héon et al., “Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25,” European Journal of Human Genetics, vol. 8, no. 1, pp. 71–74, 2000. View at Publisher · View at Google Scholar · View at Scopus
  144. D. Y. Nishimura, R. E. Swiderski, W. L. M. Alward et al., “The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25,” Nature Genetics, vol. 19, no. 2, pp. 140–147, 1998. View at Publisher · View at Google Scholar · View at Scopus
  145. T. A. Hjalt and E. V. Semina, “Current molecular understanding of Axenfeld-Rieger syndrome,” Expert Reviews in Molecular Medicine, vol. 7, no. 25, pp. 1–17, 2005. View at Publisher · View at Google Scholar · View at Scopus
  146. B. K. Ambati, M. Nozaki, N. Singh et al., “Corneal avascularity is due to soluble VEGF receptor-1,” Nature, vol. 443, no. 7114, pp. 993–997, 2006. View at Publisher · View at Google Scholar · View at Scopus
  147. C. Cursiefen, L. Chen, M. Saint-Geniez et al., “Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 30, pp. 11405–11410, 2006. View at Publisher · View at Google Scholar · View at Scopus
  148. S. Chakrabarti, M. Ramappa, S. Chaurasia, I. Kaur, and A. K. Mandal, “FOXC1-associated phenotypes in humans may not always exhibit corneal neovascularization,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. E1509, 2012. View at Publisher · View at Google Scholar
  149. J. C. Sowden, “Molecular and developmental mechanisms of anterior segment dysgenesis,” Eye, vol. 21, no. 10, pp. 1310–1318, 2007. View at Publisher · View at Google Scholar · View at Scopus
  150. L. M. Reis and E. V. Semina, “Genetics of anterior segment dysgenesis disorders,” Current Opinion in Ophthalmology, vol. 22, pp. 314–324, 2011. View at Publisher · View at Google Scholar
  151. A. Blixt, M. Mahlapuu, M. Aitola, M. Pelto-Huikko, S. Enerbäck, and P. Carlsson, “A forkhead gene, FoxE3, is essential for lens epithelial proliferation and closure of the lens vesicle,” Genes and Development, vol. 14, no. 2, pp. 245–254, 2000. View at Scopus
  152. S. K. Swamynathan, “Krüppel-like factors: three fingers in control,” Human genomics, vol. 4, no. 4, pp. 263–270, 2010. View at Scopus
  153. F. Chiambaretta, F. De Graeve, G. Turet et al., “Cell and tissue specific expression of human Krüppel-like transcription factors in human ocular surface,” Molecular Vision, vol. 10, pp. 901–909, 2004. View at Scopus
  154. H. Nakamura, J. Ueda, J. Sugar, and B. Y. J. T. Yue, “Developmentally regulated expression of Sp1 in the mouse cornea,” Investigative Ophthalmology & Visual Science, vol. 46, no. 11, pp. 4092–4096, 2005. View at Publisher · View at Google Scholar · View at Scopus
  155. R. B. Whitelock, Y. Li, L. Zhou, J. Sugar, and B. Y. J. T. Yue, “Expression of transcription factors in keratoconus, a cornea-thinning disease,” Biochemical and Biophysical Research Communications, vol. 235, no. 1, pp. 253–258, 1997. View at Publisher · View at Google Scholar · View at Scopus
  156. X. Shen, J. S. Park, Y. Qiu, J. Sugar, and B. Y. J. T. Yue, “Effects of Sp1 overexpression on cultured human corneal stromal cells,” Genes to Cells, vol. 14, no. 10, pp. 1133–1139, 2009. View at Publisher · View at Google Scholar · View at Scopus
  157. Y. Li, L. Zhou, S. S. Twining, J. Sugar, and B. Y. J. T. Yue, “Involvement of Sp1 elements in the promoter activity of the α1- proteinase inhibitor gene,” Journal of Biological Chemistry, vol. 273, no. 16, pp. 9959–9965, 1998. View at Publisher · View at Google Scholar · View at Scopus
  158. Y. Maruyama, X. Wang, Y. Li, J. Sugar, and B. Y. J. T. Yue, “Involvement of Sp1 elements in the promoter activity of genes affected in keratoconus,” Investigative Ophthalmology & Visual Science, vol. 42, no. 9, pp. 1980–1985, 2001. View at Scopus
  159. T. T. Chen, R. L. Wu, F. Castro-Munozledo, and T. T. Sun, “Regulation of K3 keratin gene transcription by Sp1 and AP-2 in differentiating rabbit corneal epithelial cells,” Molecular and Cellular Biology, vol. 17, no. 6, pp. 3056–3064, 1997. View at Scopus
  160. R. L. Wu, T. T. Chen, and T. T. Sun, “Functional importance of an Sp1- and an NFkB-related nuclear protein in a keratinocyte-specific promoter of rabbit K3 keratin gene,” Journal of Biological Chemistry, vol. 269, no. 45, pp. 28450–28459, 1994. View at Scopus
  161. O. G. Opitz and A. K. Rustgi, “Interaction between Sp1 and cell cycle regulatory proteins is important in transactivation of a differentiation-related gene,” Cancer Research, vol. 60, no. 11, pp. 2825–2830, 2000. View at Scopus
  162. G. Adhikary, J. F. Crish, R. Gopalakrishnan, F. Bone, and R. L. Eckert, “Involucrin expression in the corneal epithelium: an essential role for Sp1 transcription factors,” Investigative Ophthalmology & Visual Science, vol. 46, no. 9, pp. 3109–3120, 2005. View at Publisher · View at Google Scholar · View at Scopus
  163. M. È. Gingras, B. Masson-Gadais, K. Zaniolo et al., “Differential binding of the transcription factors Sp1, AP-1, and NFI to the promoter of the human α5 integrin gene dictates its transcriptional activity,” Investigative Ophthalmology & Visual Science, vol. 50, no. 1, pp. 57–67, 2009. View at Publisher · View at Google Scholar · View at Scopus
  164. R. Mohan, W. B. Rinehart, P. Bargagna-Mohan, and M. E. Fini, “Gelatinase B/lacZ transgenic mice, a model for mapping gelatinase B expression during developmental and injury-related tissue remodeling,” Journal of Biological Chemistry, vol. 273, no. 40, pp. 25903–25914, 1998. View at Publisher · View at Google Scholar · View at Scopus
  165. K. Takahashi and S. Yamanaka, “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors,” Cell, vol. 126, no. 4, pp. 663–676, 2006. View at Publisher · View at Google Scholar · View at Scopus
  166. J. P. Katz, N. Perreault, B. G. Goldstein et al., “The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon,” Development, vol. 129, no. 11, pp. 2619–2628, 2002. View at Scopus
  167. R. D. Young, S. K. Swamynathan, C. Boote et al., “Stromal edema in Klf4 conditional null mouse cornea is associated with altered collagen fibril organization and reduced proteoglycans,” Investigative Ophthalmology & Visual Science, vol. 50, no. 9, pp. 4155–4161, 2009. View at Publisher · View at Google Scholar · View at Scopus
  168. J. A. Segre, C. Bauer, and E. Fuchs, “Klf4 is a transcription factor required for establishing the barrier function of the skin,” Nature Genetics, vol. 22, no. 4, pp. 356–360, 1999. View at Publisher · View at Google Scholar · View at Scopus
  169. S. Swamynathan, D. Kenchegowda, J. Piatigorsky, and S. Swamynathan, “Regulation of corneal epithelial barrier function by Krüppel-like transcription factor 4,” Investigative Ophthalmology & Visual Science, vol. 52, no. 3, pp. 1762–1769, 2011. View at Publisher · View at Google Scholar · View at Scopus
  170. H. Wan, F. Luo, S. E. Wert et al., “Kruppel-like factor 5 is required for perinatal lung morphogenesis and function,” Development, vol. 135, no. 15, pp. 2563–2572, 2008. View at Publisher · View at Google Scholar · View at Scopus
  171. H. Nakamura, F. Chiambaretta, J. Sugar, V. Sapin, and B. Y. J. T. Yue, “Developmentally regulated expression of KLF6 in the mouse cornea and lens,” Investigative Ophthalmology & Visual Science, vol. 45, no. 12, pp. 4327–4332, 2004. View at Publisher · View at Google Scholar · View at Scopus
  172. F. Chiambaretta, L. Blanchon, B. Rabier et al., “Regulation of corneal keratin-12 gene expression by the human Krüppel-like transcription factor 6,” Investigative Ophthalmology & Visual Science, vol. 43, no. 11, pp. 3422–3429, 2002. View at Scopus
  173. F. Chiambaretta, H. Nakamura, F. De Graeve et al., “Krüppel-like factor 6 (KLF6) affects the promoter activity of the α1-proteinase inhibitor gene,” Investigative Ophthalmology & Visual Science, vol. 47, no. 2, pp. 582–590, 2006. View at Publisher · View at Google Scholar · View at Scopus
  174. J. G. Ilagan, A. Cvekl, M. Kantorow, J. Piatigorsky, and C. M. Sax, “Regulation of αA-crystallin gene expression: lens specificity achieved through the differential placement of similar transcriptional control elements in mouse and chicken,” Journal of Biological Chemistry, vol. 274, no. 28, pp. 19973–19978, 1999. View at Publisher · View at Google Scholar · View at Scopus
  175. K. Shirai, S. Saika, Y. Okada, E. Senba, and Y. Ohnishi, “Expression of c-Fos and c-Jun in developing mouse lens,” Ophthalmic Research, vol. 36, no. 4, pp. 226–230, 2004. View at Publisher · View at Google Scholar · View at Scopus
  176. Y. Okada, S. Saika, K. Shirai, Y. Ohnishi, and E. Senba, “Expression of AP-1 (c-Fos/c-Jun) in developing mouse corneal epithelium,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 241, no. 4, pp. 330–333, 2003. View at Scopus
  177. G. Adhikary, J. F. Crish, F. Bone, R. Gopalakrishnan, J. Lass, and R. L. Eckert, “An involucrin promoter AP1 transcription factor binding site is required for expression of involucrin in the corneal epithelium in vivo,” Investigative Ophthalmology & Visual Science, vol. 46, no. 4, pp. 1219–1227, 2005. View at Publisher · View at Google Scholar · View at Scopus
  178. D. Eckert, S. Buhl, S. Weber, R. Jäger, and H. Schorle, “The AP-2 family of transcription factors,” Genome Biology, vol. 6, no. 13, article 246, 2005. View at Publisher · View at Google Scholar · View at Scopus
  179. J. A. West-Mays, J. M. Sivak, S. S. Papagiotas et al., “Positive influence of AP-2α transcription factor on cadherin gene expression and differentiation of the ocular surface,” Differentiation, vol. 71, no. 3, pp. 206–216, 2003. View at Publisher · View at Google Scholar · View at Scopus
  180. C. Ohtaka-Maruyama, F. Hanaoka, and A. B. Chepelinsky, “A novel alternative spliced variant of the transcription factor AP2α is expressed in the murine ocular lens,” Developmental Biology, vol. 202, no. 1, pp. 125–135, 1998. View at Publisher · View at Google Scholar · View at Scopus
  181. J. A. West-Mays, J. Zhang, T. Nottoli et al., “AP-2α transcription factor is required for early morphogenesis of the lens vesicle,” Developmental Biology, vol. 206, no. 1, pp. 46–62, 1999. View at Publisher · View at Google Scholar · View at Scopus
  182. D. J. Dwivedi, G. F. Pontoriero, R. Ashery-Padan, S. Sullivan, T. Williams, and J. A. West-Mays, “Targeted deletion of AP-2α leads to disruption in corneal epithelial cell integrity and defects in the corneal stroma,” Investigative Ophthalmology & Visual Science, vol. 46, no. 10, pp. 3623–3630, 2005. View at Publisher · View at Google Scholar · View at Scopus
  183. W. Naib-Majani, W. Breipohl, E. E. Shazli et al., “The Ets-1 transcription factor is involved in pterygial angiogenesis,” Journal of Veterinary Medicine C, vol. 36, no. 2, pp. 107–110, 2007. View at Publisher · View at Google Scholar · View at Scopus
  184. N. Yoshida, S. Yoshida, M. Araie, H. Handa, and Y. I. Nabeshima, “Ets family transcription factor ESE-1 expressed in corneal epithelial cells and is involved in their differentiation,” Mechanisms of Development, vol. 97, no. 1-2, pp. 27–34, 2000. View at Publisher · View at Google Scholar · View at Scopus
  185. T. J. Liesegang, “Physiologic changes of the cornea with contact lens wear,” CLAO Journal, vol. 28, no. 1, pp. 12–27, 2002. View at Scopus
  186. R. B. Mandell and I. Fatt, “Thinning of the human cornea on awakening [20],” Nature, vol. 208, no. 5007, pp. 292–293, 1965. View at Publisher · View at Google Scholar · View at Scopus
  187. Y. Makino, R. Cao, K. Svensson et al., “Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression,” Nature, vol. 414, no. 6863, pp. 550–554, 2001. View at Publisher · View at Google Scholar · View at Scopus
  188. Y. Makino, R. Uenishi, K. Okamoto et al., “Transcriptional up-regulation of inhibitory PAS domain protein gene expression by hypoxia-inducible factor 1 (HIF-1): a negative feedback regulatory circuit in HIF-1-mediated signaling in hypoxic cells,” Journal of Biological Chemistry, vol. 282, no. 19, pp. 14073–14082, 2007. View at Publisher · View at Google Scholar · View at Scopus
  189. D. W. Nebert, A. L. Roe, M. Z. Dieter, W. A. Solis, Y. Yang, and T. P. Dalton, “Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis,” Biochemical Pharmacology, vol. 59, no. 1, pp. 65–85, 2000. View at Publisher · View at Google Scholar · View at Scopus
  190. R. B. Hough and J. Piatigorsky, “Preferential transcription of rabbit Aldh1a1 in the cornea: implication of hypoxia-related pathways,” Molecular and Cellular Biology, vol. 24, no. 3, pp. 1324–1340, 2004. View at Publisher · View at Google Scholar · View at Scopus
  191. J. S. Boesch, R. Miskimins, W. K. Miskimins, and R. Lindahl, “The same xenobiotic response element is required for constitutive and inducible expression of the mammalian aldehyde dehydrogenase-3 gene,” Archives of Biochemistry and Biophysics, vol. 361, no. 2, pp. 223–230, 1999. View at Publisher · View at Google Scholar · View at Scopus
  192. M. C. Zhang, Y. Wang, and Y. Yang, “The expression of nuclear factor κ B in inflammation-induced rat corneal neovascularization,” Ocular Immunology and Inflammation, vol. 14, no. 6, pp. 359–365, 2006. View at Publisher · View at Google Scholar · View at Scopus
  193. G. Alexander, H. Carlsen, and R. Blomhoff, “Corneal NF-κB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice,” Experimental Eye Research, vol. 82, no. 4, pp. 700–709, 2006. View at Publisher · View at Google Scholar · View at Scopus
  194. K. Kimura, S. Teranishi, K. Fukuda, K. Kawamoto, and T. Nishida, “Delayed disruption of barrier function in cultured human corneal epithelial cells induced by tumor necrosis factor-α in a manner dependent on NF-kB,” Investigative Ophthalmology & Visual Science, vol. 49, no. 2, pp. 565–571, 2008. View at Publisher · View at Google Scholar · View at Scopus
  195. G. Sosne, P. Qiu, P. L. Christopherson, and M. K. Wheater, “Thymosin beta 4 suppression of corneal NFκB: a potential anti-inflammatory pathway,” Experimental Eye Research, vol. 84, no. 4, pp. 663–669, 2007. View at Publisher · View at Google Scholar · View at Scopus
  196. G. Sosne, P. Qiu, P. L. Christopherson, and M. K. Wheater, “Thymosin beta 4 suppression of corneal NFκB: a potential anti-inflammatory pathway,” Experimental Eye Research, vol. 84, no. 4, pp. 663–669, 2007. View at Publisher · View at Google Scholar · View at Scopus
  197. M. L. Goodkin, S. Epstein, P. A. Asbell, and J. A. Blaho, “Nuclear translocation of NF-κB precedes apoptotic poly(ADP-ribose) polymerase cleavage during productive HSV-1 replication in corneal epithelial cells,” Investigative Ophthalmology & Visual Science, vol. 48, no. 11, pp. 4980–4988, 2007. View at Publisher · View at Google Scholar · View at Scopus
  198. V. Bitko, N. E. Garmon, T. Cao et al., “Activation of cytokines and NF-kappa B in corneal epithelial cells infected by respiratory syncytial virus: potential relevance in ocular inflammation and respiratory infection,” BMC Microbiology, vol. 4, article 28, 2004. View at Publisher · View at Google Scholar · View at Scopus
  199. J. Rajaiya, N. Sadeghi, and J. Chodosh, “Specific NFkappaB subunit activation and kinetics of cytokine induction in adenoviral keratitis,” Molecular vision, vol. 15, pp. 2879–2889, 2009. View at Scopus
  200. T. Orita, K. Kimura, H. Y. Zhou, and T. Nishida, “Poly(I:C)-induced adhesion molecule expression mediated by (NF)-κband phosphoinositide 3-Kinase-Akt signaling pathways in human corneal fibroblasts,” Investigative Ophthalmology & Visual Science, vol. 51, no. 11, pp. 5556–5560, 2010. View at Publisher · View at Google Scholar · View at Scopus
  201. K. Yoshida, Y. Hu, and M. Karin, “IκB kinase α is essential for development of the mammalian cornea and conjunctiva,” Investigative Ophthalmology & Visual Science, vol. 41, no. 12, pp. 3665–3669, 2000. View at Scopus
  202. M. Ueta, J. Hamuro, M. Yamamoto, K. Kaseda, S. Akira, and S. Kinoshita, “Spontaneous ocular surface inflammation and goblet cell disappearance in IκBζ gene-disrupted mice,” Investigative Ophthalmology & Visual Science, vol. 46, no. 2, pp. 579–588, 2005. View at Publisher · View at Google Scholar · View at Scopus
  203. X. Lou, S. Sun, W. Chen et al., “Negative feedback regulation of NF-κB action by CITED2 in the nucleus,” Journal of Immunology, vol. 186, no. 1, pp. 539–548, 2011. View at Publisher · View at Google Scholar · View at Scopus
  204. Y. Chen, E. C. Carlson, Z. Y. Chen et al., “Conditional deletion of Cited2 results in defective corneal epithelial morphogenesis and maintenance,” Developmental Biology, vol. 334, no. 1, pp. 243–252, 2009. View at Publisher · View at Google Scholar · View at Scopus
  205. S. J. Freedman, Z. Y. J. Sun, A. L. Kung, D. S. France, G. Wagner, and M. J. Eck, “Structural basis for negative regulation of hypoxia-inducible factor-1α by CITED2,” Nature Structural Biology, vol. 10, no. 7, pp. 504–512, 2003. View at Publisher · View at Google Scholar · View at Scopus
  206. R. Ohlsson, R. Renkawitz, and V. Lobanenkov, “CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease,” Trends in Genetics, vol. 17, no. 9, pp. 520–527, 2001. View at Publisher · View at Google Scholar · View at Scopus
  207. T. H. Kim, Z. K. Abdullaev, A. D. Smith et al., “Analysis of the Vertebrate Insulator Protein CTCF-Binding Sites in the Human Genome,” Cell, vol. 128, no. 6, pp. 1231–1245, 2007. View at Publisher · View at Google Scholar · View at Scopus
  208. T. Li and L. Lu, “Epidermal growth factor-induced proliferation requires down-regulation of Pax6 in corneal epithelial cells,” Journal of Biological Chemistry, vol. 280, no. 13, pp. 12988–12995, 2005. View at Publisher · View at Google Scholar · View at Scopus
  209. T. Li, Z. Lu, and L. Lu, “Regulation of eye development by transcription control of CCCTC Binding Factor (CTCF),” Journal of Biological Chemistry, vol. 279, no. 26, pp. 27575–27583, 2004. View at Publisher · View at Google Scholar · View at Scopus
  210. D. Wu, T. Li, Z. Lu, W. Dai, M. Xu, and L. Lu, “Effect of CTCF-binding motif on regulation of PAX6 transcription,” Investigative Ophthalmology & Visual Science, vol. 47, pp. 2422–2429, 2006. View at Publisher · View at Google Scholar
  211. T. Li and L. Lu, “Functional role of CCCTC binding factor (CTCF) in stress-induced apoptosis,” Experimental Cell Research, vol. 313, no. 14, pp. 3057–3065, 2007. View at Publisher · View at Google Scholar · View at Scopus
  212. Y. Wang and L. Lu, “Activation of oxidative stress-regulated Bcl-3 suppresses CTCF in corneal epithelial cells,” PLoS One, vol. 6, article e23984, 2011.
  213. L. Wang, S. X. Deng, and L. Lu, “Role of CTCF in EGF-induced migration of immortalized human corneal epithelial cells,” Investigative Ophthalmology & Visual Science, vol. 53, pp. 946–951, 2012. View at Publisher · View at Google Scholar
  214. J. Wang, Y. Wang, and L. Lu, “De-SUMOylation of CCCTC binding factor (CTCF) in hypoxic stress-induced human corneal epithelial cells,” The Journal of Biological Chemistry, vol. 287, pp. 12469–12479, 2012. View at Publisher · View at Google Scholar
  215. N. Hahn, C. T. Dietz, S. Kuhl, U. Vossmerbaeumer, and J. Kroll, “KLEIP deficiency in mice causes progressive corneal neovascular dystrophy,” Investigative Ophthalmology & Visual Science, vol. 53, pp. 3260–3268, 2012. View at Publisher · View at Google Scholar
  216. A. M. Verdoni, N. Aoyama, A. Ikeda, and S. Ikeda, “Effect of destrin mutations on the gene expression profile in vivo,” Physiological Genomics, vol. 34, no. 1, pp. 9–21, 2008. View at Publisher · View at Google Scholar · View at Scopus
  217. R. S. Smith, N. L. Hawes, S. D. Kuhlmann et al., “Corn1: a mouse model for corneal surface disease and neovascularization,” Investigative Ophthalmology & Visual Science, vol. 37, no. 2, pp. 397–404, 1996. View at Scopus
  218. I. J. Wang, C. W. C. Kao, C. Y. Liu et al., “Characterization of Corn1 Mice: alteration of epithelial and stromal cell gene expression,” Molecular Vision, vol. 7, pp. 20–26, 2001. View at Scopus
  219. S. Ikeda, L. A. Cunningham, D. Boggess, et al., “Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor),” Human Molecular Genetics, vol. 12, pp. 1029–1037, 2003. View at Publisher · View at Google Scholar
  220. C. Cursiefen, S. Ikeda, P. M. Nishina et al., “Spontaneous corneal hem- and lymphangiogenesis in mice with destrin-mutation depend on VEGFR3 signaling,” American Journal of Pathology, vol. 166, no. 5, pp. 1367–1377, 2005. View at Scopus
  221. A. M. Verdoni, R. S. Smith, A. Ikeda, and S. Ikeda, “Defects in actin dynamics lead to an autoinflammatory condition through the upregulation of CXCL5,” PLoS ONE, vol. 3, no. 7, article e2701, Article ID e2701, 2008. View at Publisher · View at Google Scholar · View at Scopus
  222. A. M. Verdoni, K. J. Schuster, B. S. Cole, A. Ikeda, W. W. Kao, and S. Ikeda, “A pathogenic relationship between a regulator of the actin cytoskeleton and serum response factor,” Genetics, vol. 186, no. 1, pp. 147–157, 2010. View at Publisher · View at Google Scholar · View at Scopus
  223. S. K. Swamynathan, M. A. Crawford, W. G. Robison, J. Kanungo, and J. Piatigorsky, “Adaptive differences in the structure and macromolecular compositions of the air and water corneas of the "four-eyed" fish (Anableps anableps),” FASEB Journal, vol. 17, no. 14, pp. 1996–2005, 2003. View at Publisher · View at Google Scholar · View at Scopus
  224. S. Jia, M. Omelchenko, D. Garland et al., “Duplicated gelsolin family genes in zebrafish: a novel scinderin-like gene (scinla) encodes the major corneal crystallin,” FASEB Journal, vol. 21, no. 12, pp. 3318–3328, 2007. View at Publisher · View at Google Scholar · View at Scopus
  225. J. Kanungo, S. K. Swamynathan, and J. Piatigorsky, “Abundant corneal gelsolin in Zebrafish and the “four-eyed” fish, Anableps anableps: possible analogy with multifunctional lens crystallins,” Experimental Eye Research, vol. 79, no. 6, pp. 949–956, 2004. View at Publisher · View at Google Scholar · View at Scopus
  226. J. Kanungo, Z. Kozmik, S. K. Swamynathan, and J. Piatigorsky, “Gelsolin is a dorsalizing factor in zebrafish,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 6, pp. 3287–3292, 2003. View at Publisher · View at Google Scholar · View at Scopus
  227. J. P. Solomon, L. J. Page, W. E. Balch, and J. W. Kelly, “Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention,” Critical Reviews in Biochemistry and Molecular Biology, vol. 47, pp. 282–296, 2012. View at Publisher · View at Google Scholar
  228. M. E. Rosenberg, T. M. T. Tervo, J. Gallar et al., “Corneal morphology and sensitivity in lattice dystrophy type II (familial amyloidosis, Finnish type),” Investigative Ophthalmology & Visual Science, vol. 42, no. 3, pp. 634–641, 2001. View at Scopus
  229. C. P. J. Maury, “Finnish amyloidosis: from protein to gene,” Journal of Internal Medicine, vol. 230, no. 3, pp. 193–194, 1991. View at Scopus
  230. C. P. J. Maury, “Gelsolin-related amyloidosis. Identification of the amyloid protein in Finnish hereditary amyloidosis as a fragment of variant gelsolin,” Journal of Clinical Investigation, vol. 87, no. 4, pp. 1195–1199, 1991. View at Scopus
  231. W. T. Kays and J. Piatigorsky, “Aldehyde dehydrogenase class 3 expression: identification of a cornea-preferred gene promoter in transgenic mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 25, pp. 13594–13599, 1997. View at Scopus
  232. J. Davis, D. Davis, B. Norman, and J. Piatigorsky, “Gene expression of the mouse corneal crystallin Aldh3a1: activation by Pax6, Oct1, and p300,” Investigative Ophthalmology & Visual Science, vol. 49, no. 5, pp. 1814–1826, 2008. View at Publisher · View at Google Scholar · View at Scopus
  233. R. Manzer, L. Qamar, T. Estey, A. Pappa, D. R. Petersen, and V. Vasiliou, “Molecular cloning and baculovirus expression of the rabbit corneal aldehyde dehydrogenase (ALDH1A1) cDNA,” DNA and Cell Biology, vol. 22, no. 5, pp. 329–338, 2003. View at Publisher · View at Google Scholar · View at Scopus
  234. C. M. Sax, C. Salamon, W. T. Kays et al., “Transketolase is a major protein in the mouse cornea,” Journal of Biological Chemistry, vol. 271, no. 52, pp. 33568–33574, 1996. View at Publisher · View at Google Scholar · View at Scopus
  235. C. M. Sax, W. T. Kays, C. Salamon, M. M. Chervenak, Y. S. Xu, and J. Piatigorsky, “Transketolase gene expression in the cornea is influenced by environmental factors and developmentally controlled events,” Cornea, vol. 19, no. 6, pp. 833–841, 2000. View at Publisher · View at Google Scholar · View at Scopus
  236. W. W. Y. Kao, C. Y. Liu, R. L. Converse et al., “Keratin 12-deficient mice have fragile corneal epithelia,” Investigative Ophthalmology & Visual Science, vol. 37, no. 13, pp. 2572–2584, 1996. View at Scopus
  237. A. Shiraishi, R. L. Converse, C. Y. Liu, F. Zhou, C. W. C. Kao, and W. W. Y. Kao, “Identification of the cornea-specific keratin 12 promoter by in vivo particle-mediated gene transfer,” Investigative Ophthalmology & Visual Science, vol. 39, no. 13, pp. 2554–2561, 1998. View at Scopus
  238. J. J. Liu, W. W. Y. Kao, and S. E. Wilson, “Corneal epithelium-specific mouse keratin K12 promoter,” Experimental Eye Research, vol. 68, no. 3, pp. 295–301, 1999. View at Publisher · View at Google Scholar · View at Scopus
  239. S. Chakravarti, T. Magnuson, J. H. Lass, K. J. Jepsen, C. LaMantia, and H. Carroll, “Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican,” Journal of Cell Biology, vol. 141, no. 5, pp. 1277–1286, 1998. View at Publisher · View at Google Scholar · View at Scopus
  240. S. Ying, A. Shiraishi, C. W. C. Kao et al., “Characterization and expression of the mouse lumican gene,” Journal of Biological Chemistry, vol. 272, no. 48, pp. 30306–30313, 1997. View at Publisher · View at Google Scholar · View at Scopus
  241. S. Chakravarti, W. M. Petroll, J. R. Hassell et al., “Corneal opacity in lumican-null mice: defects in collagen fibril structure and packing in the posterior stroma,” Investigative Ophthalmology & Visual Science, vol. 41, no. 11, pp. 3365–3373, 2000. View at Scopus
  242. S. Chakravarti, G. Zhang, I. Chervoneva, L. Roberts, and D. E. Birk, “Collagen fibril assembly during postnatal development and dysfunctional regulation in the lumican-deficient murine cornea,” Developmental Dynamics, vol. 235, no. 9, pp. 2493–2506, 2006. View at Publisher · View at Google Scholar · View at Scopus
  243. S. Lee, K. Bowrin, A. R. Hamad, and S. Chakravarti, “Extracellular matrix lumican deposited on the surface of neutrophils promotes migration by binding to β2 integrin,” Journal of Biological Chemistry, vol. 284, no. 35, pp. 23662–23669, 2009. View at Publisher · View at Google Scholar · View at Scopus
  244. K. Lohr, H. Sardana, S. Lee, et al., “Extracellular matrix protein lumican regulates inflammation in a mouse model of colitis,” Inflammatory Bowel Diseases, vol. 18, pp. 143–151, 2012. View at Publisher · View at Google Scholar
  245. A. J. Quantock, K. M. Meek, and S. Chakravarti, “An x-ray diffraction investigation of corneal structure in lumican-deficient mice,” Investigative Ophthalmology & Visual Science, vol. 42, no. 8, pp. 1750–1756, 2001. View at Scopus
  246. H. Shao, S. Lee, S. Gae-Scott, et al., “Extracellular matrix lumican promotes bacterial phagocytosis and Lum-/- mice show increased Pseudomonas aeruginosa lung infection severity,” The Journal of Biological Chemistry, vol. 287, no. 43, pp. 35860–35872, 2012. View at Publisher · View at Google Scholar
  247. F. Wu, N. Vij, L. Roberts, S. Lopez-Briones, S. Joyce, and S. Chakravarti, “A novel role of the lumican core protein in bacterial lipopolysaccharide- induced innate immune response,” Journal of Biological Chemistry, vol. 282, no. 36, pp. 26409–26417, 2007. View at Publisher · View at Google Scholar · View at Scopus
  248. E. C. Carlson, C. Y. Liu, T. I. Chikama et al., “Keratocan, a cornea-specific keratan sulfate proteoglycan, is regulated by lumican,” Journal of Biological Chemistry, vol. 280, no. 27, pp. 25541–25547, 2005. View at Publisher · View at Google Scholar · View at Scopus
  249. C. Y. Liu, D. E. Birk, J. R. Hassell, B. Kane, and W. W. Y. Kao, “Keratocan-deficient mice display alterations in corneal structure,” Journal of Biological Chemistry, vol. 278, no. 24, pp. 21672–21677, 2003. View at Publisher · View at Google Scholar · View at Scopus
  250. C. Y. Liu, A. Shiraishi, C. W. C. Kao et al., “The cloning of mouse keratocan cDNA and genomic DNA and the characterization of its expression during eye development,” Journal of Biological Chemistry, vol. 273, no. 35, pp. 22584–22588, 1998. View at Publisher · View at Google Scholar · View at Scopus
  251. C. Y. Liu, H. Arar, C. Kao, and W. W. Y. Kao, “Identification of a 3.2 kb 5'-flanking region of the murine keratocan gene that directs β-galactosidase expression in the adult corneal stroma of transgenic mice,” Gene, vol. 250, no. 1-2, pp. 85–96, 2000. View at Publisher · View at Google Scholar · View at Scopus
  252. O. Dahan, H. Gingold, and Y. Pilpel, “Regulatory mechanisms and networks couple the different phases of gene expression,” Trends in Genetics, vol. 27, no. 8, pp. 316–322, 2011. View at Publisher · View at Google Scholar · View at Scopus
  253. A. R. Morris, N. Mukherjee, and J. D. Keene, “Systematic analysis of posttranscriptional gene expression,” Wiley Interdisciplinary Reviews, vol. 2, no. 2, pp. 162–180, 2010. View at Publisher · View at Google Scholar · View at Scopus