The long-term goal of this project is to understand the molecular basis of corneal epithelial differentiation. To accomplish this goal, a combination of cell culture, monoclonal antibody and recombinant DNA techniques will be used to study three separate but closely related projects. 1. To study the mechanisms underlying the differential expression of keratin proteins in rabbit corneal epithelium by: (a) Determining whether the synthesis of the 48K/56K hyperproliferation-related keratin pair is regulated translationally; (b) Isolating and characterizing appropriate cDNA probes for the 48K/56K and the 55K/64K corneal differentiation keratins; (c) Using these cDNA probes to study transcriptional and post-transcriptional regulation of keratin synthesis; and (d) Isolating the genes of 55K/64K rabbit corneal epithelial keratins to study the mechanism of their tissue-specificity and """"""""paired"""""""" coexpression. 2. To study the possible role of basement membrane (BM) heterogeneity in regulating keratin expression in corneal epithelium by: (a) Generating a panel of monoclonal antibodies whose heterogeneous staining with corneal and limbal BM correlates with the basal expression of 64K keratin; and (b) Studying the structure and possible function of these novel basement membrane components. 3. To study the transdifferentiation of conjunctival to corneal epithelium by: (a) Asking whether adult or embryonic conjunctival epithelium can be induced by corneal stroma to become a bona fide corneal epithelium as defined by the expression of the 64K corneal keratin; and (b) Comparing the behavior of corneal and conjunctival epithelial cells under identical cell culture conditions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004722-09
Application #
3259179
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1982-08-01
Project End
1993-04-30
Budget Start
1990-05-01
Budget End
1991-04-30
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost
Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
Sun, Tung-Tien; Lavker, Robert M (2004) Corneal epithelial stem cells: past, present, and future. J Investig Dermatol Symp Proc 9:202-7
Lavker, R M; Wei, Z G; Sun, T T (1998) Phorbol ester preferentially stimulates mouse fornical conjunctival and limbal epithelial cells to proliferate in vivo. Invest Ophthalmol Vis Sci 39:301-7
Chen, T T; Wu, R L; Castro-Munozledo, F et al. (1997) Regulation of K3 keratin gene transcription by Sp1 and AP-2 in differentiating rabbit corneal epithelial cells. Mol Cell Biol 17:3056-64
Wei, Z G; Lin, T; Sun, T T et al. (1997) Clonal analysis of the in vivo differentiation potential of keratinocytes. Invest Ophthalmol Vis Sci 38:753-61
Wei, Z G; Sun, T T; Lavker, R M (1996) Rabbit conjunctival and corneal epithelial cells belong to two separate lineages. Invest Ophthalmol Vis Sci 37:523-33
Wei, Z G; Cotsarelis, G; Sun, T T et al. (1995) Label-retaining cells are preferentially located in fornical epithelium: implications on conjunctival epithelial homeostasis. Invest Ophthalmol Vis Sci 36:236-46
Wu, R L; Chen, T T; Sun, T T (1994) Functional importance of an Sp1- and an NFkB-related nuclear protein in a keratinocyte-specific promoter of rabbit K3 keratin gene. J Biol Chem 269:28450-9
Wu, R L; Zhu, G; Galvin, S et al. (1994) Lineage-specific and differentiation-dependent expression of K12 keratin in rabbit corneal/limbal epithelial cells: cDNA cloning and northern blot analysis. Differentiation 55:137-44
Wei, Z G; Wu, R L; Lavker, R M et al. (1993) In vitro growth and differentiation of rabbit bulbar, fornix, and palpebral conjunctival epithelia. Implications on conjunctival epithelial transdifferentiation and stem cells. Invest Ophthalmol Vis Sci 34:1814-28
Pang, Y Y; Schermer, A; Yu, J et al. (1993) Suprabasal change and subsequent formation of disulfide-stabilized homo- and hetero-dimers of keratins during esophageal epithelial differentiation. J Cell Sci 104 ( Pt 3):727-40

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