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Yuk Fai Leung, Liyun Zhang, Wenxuan Zhong; Genomic Analysis of Zebrafish Retinal Pigment Epithelium (RPE) Differentiation and Paracrine Signal Transduction. Invest. Ophthalmol. Vis. Sci. 2011;52(14):25.
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While the dysfunction of retinal pigment epithelium (RPE) leads to many retinal degeneration diseases, the genes that control its differentiation and mediate its paracrine signal transduction are poorly understood. The purpose of this study was to establish a genomic approach for identifying genes that control RPE-specific differentiation and potential paracrine signals specifically secreted by RPE in zebrafish retinal dystrophic mutants.
An ultrastructural analysis by transmission electron microscopy (TEM) was conducted on a mutant young (yng), which has been reported to have retinal terminal differentiation problems due to a null mutation in brg1. The mutant also shows several RPE developmental defects. To identify underlying genes that are specifically perturbed in yng RPE, we first obtained gene expression profiles of whole embryos, retinas and RPE-attached retinas between wild-type (WT) and yng at 52 hours post-fertilization (hpf), during which the RPE defects and the retinal differentiation issues became apparent. Then, a factorial analysis was established to investigate the effect of tissue type and mutation on gene expression.
Several RPE defects in yng were identified by histology, which include fewer and abnormally distributed melanosomes, and irregularly shaped nuclei. Factorial microarray analysis showed that 392 genes were specifically regulated by Brg1 in the RPE, 362 genes were specifically regulated by Brg1 in the retina, and 39 genes were regulated by Brg1 in both RPE and retina. A number of these Brg1-regulated RPE-specific genes are related to cytoskeletal dynamics, signal transduction and transcriptional regulation of RPE development. In particular, several bmp and wnt-related paracrine signaling genes were identified.
This study has identified potential gene candidates for RPE development and paracrine signals secreted by RPE, which may play a critical role in RPE and/or retinal development. The results have also demonstrated the utility of a designed microarray experiment for identifying such key molecular determinants in a complex zebrafish eye organ.
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