Requirement for Pax6 in corneal morphogenesis: a role in adhesion

被引:127
作者
Davis, J
Duncan, MK
Robison, WG
Piatigorsky, J [1 ]
机构
[1] NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA
[2] Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA
[3] NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA
关键词
Pax6; cornea; adhesion; SEY mice; development;
D O I
10.1242/jcs.00441
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The Pax6 transcription factor functions early during embryogenesis to control key steps in brain, pancreas, olfactory and ocular system development. A. requirement for Pax6 in proper formation of lens, iris and retina is well documented. By examining the corneas of heterozygous Small eye (SEY) mice, this report shows that Pax6 is also necessary for normal corneal morphogenesis. In particular, the epithelial component of the postnatal and adult SEY (+/-) cornea is thinner owing to a reduction in the number of cell layers, despite a tenfold increase in the proliferative index and no change in TUNEL labeling. Ultrastructural views revealed large gaps between corneal epithelial cells and a change in the appearance of desmosomes, suggesting that adhesion abnormalities contribute to the corneal phenotype of SEY (+/-) mice. Western blot analysis and immunofluorescence showed equivalent amounts and normal localization of E-cadherin in SEY (+/-) corneas, and the actin cytoskeleton appeared normal as judged by phalloidin staining. By contrast, the levels of desmoglein, beta-catenin and gamma-catenin were reduced in the SEY (+/-) cornea. In addition, the amount of keratin-12 mRNA and protein, the major intermediate filament, was reduced in SEY (+/-) corneal epithelium as shown by in situ hybridization and immunohistochemistry. Finally, the SEY (+/-) corneal epithelium adheres less well than wild-type when challenged with gentle rubbing using a microsponge. In conclusion, our results indicate that cellular adhesion is compromised in the SEY (+/-) corneal epithelium and suggests a role for Pax6 in the proper generation and maintenance of the adult cornea.
引用
收藏
页码:2157 / 2167
页数:11
相关论文
共 105 条
  • [1] Albert DM, 1994, PRINCIPLES PRACTICE
  • [2] Mice expressing a mutant desmosomal cadherin exhibit abnormalities in desmosomes, proliferation, and epidermal differentiation
    Allen, E
    Yu, QC
    Fuchs, E
    [J]. JOURNAL OF CELL BIOLOGY, 1996, 133 (06) : 1367 - 1382
  • [3] Angst BD, 2001, J CELL SCI, V114, P629
  • [4] Pax6 lights-up the way for eye development
    Ashery-Padan, R
    Gruss, P
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2001, 13 (06) : 706 - 714
  • [5] Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye
    Ashery-Padan, R
    Marquardt, T
    Zhou, XL
    Gruss, P
    [J]. GENES & DEVELOPMENT, 2000, 14 (21) : 2701 - 2711
  • [6] The lens organizes the anterior segment: Specification of neural crest cell differentiation in the avian eye
    Beebe, DC
    Coats, JM
    [J]. DEVELOPMENTAL BIOLOGY, 2000, 220 (02) : 424 - 431
  • [7] Bierkamp C, 1999, DEVELOPMENT, V126, P371
  • [8] A vector for expressing foreign genes in the brains and hearts of transgenic mice
    Borchelt, DR
    Davis, J
    Fischer, M
    Lee, MK
    Slunt, HH
    Ratovitsky, T
    Regard, J
    Copeland, NG
    Jenkins, NA
    Sisodia, SS
    Price, DL
    [J]. GENETIC ANALYSIS-BIOMOLECULAR ENGINEERING, 1996, 13 (06): : 159 - 163
  • [9] The small-eye mutation results in abnormalities in the lateral cortical migratory stream
    Brunjes, PC
    Fisher, M
    Grainger, R
    [J]. DEVELOPMENTAL BRAIN RESEARCH, 1998, 110 (01): : 121 - 125
  • [10] Pax-6 in development and evolution
    Callaerts, P
    Halder, G
    Gehring, WJ
    [J]. ANNUAL REVIEW OF NEUROSCIENCE, 1997, 20 : 483 - 532