The goal of this proposal is to determine the role and regulation of specific adhesion related molecules in the maintenance of corneal epithelial integrity. The cells of the corneal epithelium are tightly adherent to each other as well as to the underlying extracellular matrix. To maintain a healthy epithelium the cells must regulate their adhesivity. The balance between stable and dynamic epithelial adhesion cell-cell and cell matrix adhesion is well demonstrated during the process of epithelial wound healing. While the epithelial cell sheet remains intact during migration its adhesions are modified in such a way to afford cell shape changes, cell sliding and cell spreading. Upon successful completion of the wound closure, the epithelium reverses the above changes and again establishes the stable epithelial configuration. The investigator plans to further characterize an adhesion related protein, pinin, that may be integral to regulating epithelial phenotype. The goal is to address the consequences of over and/or underexpressing pinin and look at the gene expression downstream of pinin and determine the molecular complexes with which pinin is associated.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007883-15
Application #
6635606
Study Section
Special Emphasis Panel (ZRG1-SSS-R (03))
Program Officer
Fisher, Richard S
Project Start
1988-12-01
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
15
Fiscal Year
2003
Total Cost
$326,250
Indirect Cost
Name
University of Florida
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Akin, Debra; Newman, Jeremy R B; McIntyre, Lauren M et al. (2016) RNA-seq analysis of impact of PNN on gene expression and alternative splicing in corneal epithelial cells. Mol Vis 22:40-60
Joo, Jeong Hoon; Ryu, Danny; Peng, Qian et al. (2014) Role of Pnn in alternative splicing of a specific subset of lncRNAs of the corneal epithelium. Mol Vis 20:1629-42
Joo, Jeong-Hoon; Correia, Greg P; Li, Jian-Liang et al. (2013) Transcriptomic analysis of PNN- and ESRP1-regulated alternative pre-mRNA splicing in human corneal epithelial cells. Invest Ophthalmol Vis Sci 54:697-707
Xu, Yufei; Xu, Chao; Kato, Akiko et al. (2012) Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development. Cell 151:1200-13
Joo, Jeong-Hoon; Kim, Yong H; Dunn, Nicholas W et al. (2010) Disruption of mouse corneal epithelial differentiation by conditional inactivation of pnn. Invest Ophthalmol Vis Sci 51:1927-34
Joo, Jeong-Hoon; Taxter, Timothy J; Munguba, Gustavo C et al. (2010) Pinin modulates expression of an intestinal homeobox gene, Cdx2, and plays an essential role for small intestinal morphogenesis. Dev Biol 345:191-203
Alpatov, Roman; Shi, Yujiang; Munguba, Gustavo C et al. (2008) Corepressor CtBP and nuclear speckle protein Pnn/DRS differentially modulate transcription and splicing of the E-cadherin gene. Mol Cell Biol 28:1584-95
Joo, Jeong-Hoon; Lee, Young Jae; Munguba, Gustavo C et al. (2007) Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice. Dev Dyn 236:2147-58
Joo, Jeong-Hoon; Alpatov, Roman; Munguba, Gustavo C et al. (2005) Reduction of Pnn by RNAi induces loss of cell-cell adhesion between human corneal epithelial cells. Mol Vis 11:133-42
Alpatov, Roman; Munguba, Gustavo Costa; Caton, Paul et al. (2004) Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene. Mol Cell Biol 24:10223-35

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