The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 8 Apr 2003
doi: 10.1242/jcs.00441
Research Article
Requirement for Pax6 in corneal morphogenesis: a role in adhesion
Janine Davis,
Melinda K. Duncan,
W. Gerald Robison Jr,
and
Joram Piatigorsky*
* Author for correspondence (e-mail: joramp{at}nei.nih.gov)
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, 
-catenin and 
-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.
This article has been cited by other articles:
|
|
|
|
 
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
Invest. Ophthalmol. Vis. Sci.,
August 1, 2008;
49(8):
3360 - 3370.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Davis, D. Davis, B. Norman, and J. Piatigorsky
Gene Expression of the Mouse Corneal Crystallin Aldh3a1: Activation by Pax6, Oct1, and p300
Invest. Ophthalmol. Vis. Sci.,
May 1, 2008;
49(5):
1814 - 1826.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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
Mol. Cell. Biol.,
January 1, 2007;
27(1):
182 - 194.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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
Invest. Ophthalmol. Vis. Sci.,
December 1, 2006;
47(12):
5276 - 5282.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Ouyang, Y.-C. Shen, L.-K. Yeh, W. Li, B. M. Coyle, C.-Y. Liu, and M. E. Fini
Pax6 overexpression suppresses cell proliferation and retards the cell cycle in corneal epithelial cells.
Invest. Ophthalmol. Vis. Sci.,
June 1, 2006;
47(6):
2397 - 2407.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mukhopadhyay, M. Gorivodsky, S. Shtrom, A. Grinberg, C. Niehrs, M. I. Morasso, and H. Westphal
Dkk2 plays an essential role in the corneal fate of the ocular surface epithelium
Development,
June 1, 2006;
133(11):
2149 - 2154.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ramaesh, K. Ramaesh, R. Leask, A. Springbett, S. C. Riley, B. Dhillon, and J. D. West
Increased Apoptosis and Abnormal Wound-Healing Responses in the Heterozygous Pax6+/- Mouse Cornea
Invest. Ophthalmol. Vis. Sci.,
May 1, 2006;
47(5):
1911 - 1917.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Dwivedi, G. F. Pontoriero, R. Ashery-Padan, S. Sullivan, T. Williams, and J. A. West-Mays
Targeted Deletion of AP-2{alpha} Leads to Disruption in Corneal Epithelial Cell Integrity and Defects in the Corneal Stroma
Invest. Ophthalmol. Vis. Sci.,
October 1, 2005;
46(10):
3623 - 3630.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yoshida, S. Shimmura, J. Shimazaki, N. Shinozaki, and K. Tsubota
Serum-Free Spheroid Culture of Mouse Corneal Keratocytes
Invest. Ophthalmol. Vis. Sci.,
May 1, 2005;
46(5):
1653 - 1658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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
Invest. Ophthalmol. Vis. Sci.,
December 1, 2004;
45(12):
4327 - 4332.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. K. Duncan, L. Xie, L. L. David, M. L. Robinson, J. R. Taube, W. Cui, and L. W. Reneker
Ectopic Pax6 Expression Disturbs Lens Fiber Cell Differentiation
Invest. Ophthalmol. Vis. Sci.,
October 1, 2004;
45(10):
3589 - 3598.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. J. Lovicu, P. Steven, S. Saika, and J. W. McAvoy
Aberrant Lens Fiber Differentiation in Anterior Subcapsular Cataract Formation: A Process Dependent on Reduced Levels of Pax6
Invest. Ophthalmol. Vis. Sci.,
June 1, 2004;
45(6):
1946 - 1953.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Collinson, S. A. Chanas, R. E. Hill, and J. D. West
Corneal Development, Limbal Stem Cell Function, and Corneal Epithelial Cell Migration in the Pax6+/- Mouse
Invest. Ophthalmol. Vis. Sci.,
April 1, 2004;
45(4):
1101 - 1108.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2003
