Retinal engineering is likely to be the ultimate cure for blinding disorders caused by degeneration of retinal cells. A prerequisite for retinal engineering is understanding the mechanisms of cellular pattern formation in the vertebrate retina. Our long-term research interest is to define these mechanisms. Recent studies suggest that the polarity of the retinal epithelia plays an essential role in neural retinal pattern formation; but the mechanisms involved are largely unknown. We have shown that three zebrafish polarity genes (nok, Pard3, and zLinT) are required to establish the cellular architecture of the mature retina. These proteins all contain well-established protein-protein interaction domains. Our data suggest that zLin7 likely interacts with Nok and that Nok is required for the interactions between the neural retina and the juxtaposed retinal pigmented epithelium (RPE). Our central hypothesis is that Nok, Pard3, and zLin7 associate with other proteins in a developmentally regulated fashion to collectively establish and/or maintain the proper polarity of retinal epithelia and consequently ensure accurate interactions between the neural retina and RPE. These interactions likely enable the proper distribution of cell migration cues required for retinal pattern formation. The major aims of the research to be pursued in this project include: 1) Determine to what extent Nok's function in controlling cellular pattern formation in the neural retina requires Nok's activity in the RPE by making and analyzing transgenic embryos that display mosaic Nok expressions in the eye; 2) Determine whether Nok physically interacts with one or more isoforms of zLin7's and what protein domains are involved in the interaction; 3) Identify and characterize the proteins that interact with Nok, Pard3, and zLin7 complexes during retinal development by using affinity purification, yeast two-hybrid, and candidate genes approaches. ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY016099-01A1
Application #
6969518
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Mariani, Andrew P
Project Start
2005-09-30
Project End
2010-08-31
Budget Start
2005-09-30
Budget End
2006-08-31
Support Year
1
Fiscal Year
2005
Total Cost
$325,286
Indirect Cost
Name
University of Pittsburgh
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Guo, Chuanyu; Zou, Jian; Wen, Yi et al. (2018) Apical Cell-Cell Adhesions Reconcile Symmetry and Asymmetry in Zebrafish Neurulation. iScience 3:63-85
Fu, Jinling; Nagashima, Mikiko; Guo, Chuanyu et al. (2018) Novel Animal Model of Crumbs-Dependent Progressive Retinal Degeneration That Targets Specific Cone Subtypes. Invest Ophthalmol Vis Sci 59:505-518
Fang, Wei; Guo, Chuanyu; Wei, Xiangyun (2017) Rainbow Enhancers Regulate Restrictive Transcription in Teleost Green, Red, and Blue Cones. J Neurosci 37:2834-2848
Fang, Wei; Bonaffini, Sarah; Zou, Jian et al. (2013) Characterization of transgenic zebrafish lines that express GFP in the retina, pineal gland, olfactory bulb, hatching gland, and optic tectum. Gene Expr Patterns 13:150-9
Fu, Jinling; Fang, Wei; Zou, Jian et al. (2013) A robust procedure for distinctively visualizing zebrafish retinal cell nuclei under bright field light microscopy. J Histochem Cytochem 61:248-56
Zou, Jian; Wen, Yi; Yang, Xiaojun et al. (2013) Spatial-temporal expressions of Crumbs and Nagie oko and their interdependence in zebrafish central nervous system during early development. Int J Dev Neurosci 31:770-82
Zou, Jian; Wang, Xiaolei; Wei, Xiangyun (2012) Crb apical polarity proteins maintain zebrafish retinal cone mosaics via intercellular binding of their extracellular domains. Dev Cell 22:1261-74
Zou, Jian; Yang, Xiaojun; Wei, Xiangyun (2010) Restricted localization of ponli, a novel zebrafish MAGUK-family protein, to the inner segment interface areas between green, red, and blue cones. Invest Ophthalmol Vis Sci 51:1738-46
Zou, Jian; Wei, Xiangyun (2010) Transplantation of GFP-expressing blastomeres for live imaging of retinal and brain development in chimeric zebrafish embryos. J Vis Exp :
Yang, Xiaojun; Zou, Jian; Hyde, David R et al. (2009) Stepwise maturation of apicobasal polarity of the neuroepithelium is essential for vertebrate neurulation. J Neurosci 29:11426-40

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