The underlying cause of cataracts can often be shown to involve defects in lens fiber cell differentiation. The proposal seeks to elucidate the mechanisms controlling the high level, lens-specific expression of the bB1 crystallin gene, a crystallin expressed exclusively in differentiating lens fiber cells.
The aims of the proposal are to determine the role of the Prox-1 homeodomain protein in activation of the bB1 gene, to determine the role of Pax6-mediated repression of bB1 promoter in fiber cell differentiation, to identify other transcription factors that are involved in regulating expression of the bB1 gene and finally to identify sequences in the bB1 crystallin gene promoter that are required for appropriate spatial and temporal expression of bB1 crystallin during fiber cell differentiation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012221-05
Application #
6518600
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Liberman, Ellen S
Project Start
1998-07-01
Project End
2003-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
5
Fiscal Year
2002
Total Cost
$298,237
Indirect Cost
Name
University of Delaware
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716
Audette, Dylan S; Scheiblin, David A; Duncan, Melinda K (2017) The molecular mechanisms underlying lens fiber elongation. Exp Eye Res 156:41-49
Audette, Dylan S; Anand, Deepti; So, Tammy et al. (2016) Prox1 and fibroblast growth factor receptors form a novel regulatory loop controlling lens fiber differentiation and gene expression. Development 143:318-28
Manthey, Abby L; Terrell, Anne M; Wang, Yan et al. (2014) The Zeb proteins ?EF1 and Sip1 may have distinct functions in lens cells following cataract surgery. Invest Ophthalmol Vis Sci 55:5445-55
Manthey, Abby L; Terrell, Anne M; Lachke, Salil A et al. (2014) Development of novel filtering criteria to analyze RNA-sequencing data obtained from the murine ocular lens during embryogenesis. Genom Data 2:369-374
Manthey, Abby L; Lachke, Salil A; FitzGerald, Paul G et al. (2014) Loss of Sip1 leads to migration defects and retention of ectodermal markers during lens development. Mech Dev 131:86-110
Chatterjee, Sharmila; Wang, Yan; Duncan, Melinda K et al. (2013) Junctional adhesion molecule-A regulates vascular endothelial growth factor receptor-2 signaling-dependent mouse corneal wound healing. PLoS One 8:e63674
Grabitz, Abby L; Duncan, Melinda K (2012) Focus on molecules: Smad Interacting Protein 1 (Sip1, ZEB2, ZFHX1B). Exp Eye Res 101:105-6
Parthasarathy, Geetha; Ma, Bo; Zhang, Cheng et al. (2011) Expression of ?A3/A1-crystallin in the developing and adult rat eye. J Mol Histol 42:59-69
Duncan, Melinda K (2011) Development. A new focus on RNA in the lens. Science 331:1523-4
Chen, Xiaoren; Taube, Jennifer R; Simirskii, Vladimir I et al. (2008) Dual roles for Prox1 in the regulation of the chicken betaB1-crystallin promoter. Invest Ophthalmol Vis Sci 49:1542-52

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