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S. Satoh, M. Inoue, A. Iida, T. Kodama, S. Watanabe; Regulation of Mouse Retinal Development by a Network of Nuclear Receptors. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2916.
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© ARVO (1962-2015); The Authors (2016-present)
Nuclear receptors are ligand-dependent transcriptional regulators that play pivotal roles in various organogenesis. Although importance of some nuclear receptors had been reported, comprehensive analysis of the role of nuclear receptors for retinal development has not been done. We aimed to reveal the expression patterns of nuclear receptors in retinal development systematically. Then we focused on a COUP-TFs nucelar receptors subfamily of their functions in retinal development.
By using a panel of antibodies for nuclear receptors, we analyzed transition of the expression of nuclear receptors along with mouse retinal development. Then, functional analyses by overexpression and knock down were done in retinal explant culture using retrovirus-mediated gene expression systems.
We found unique spatio-temporal expression patterns of various nuclear receptors during retinal development. Among them, COUP-TF family members are very unique since they expressed axis specific manner. COUP-TFI was expressed broadly in retina with gradient of signal strength in dorsal/ventral axis. After birth, its expression becomes restricted to be in INL and GCL. COUP-TFII was specifically found in a subset of amacrine cells at ventral side but broadly expressed at dorsal side at all stages examined. Ear2 (COUP-TFIII) was expressed specifically in horizontal cells during retinal development and in adulthood. In addition, Ear2 was expressed in postnatal cone cells at the region from center to ventral side. Gain and loss of functions of COUP-TFs in retinal explant culture indicate roles of COUP-TFs in certain cell differentiation. In vivo analyses of retina development are currently undertaken by using COUP-TFII conditional knockout mouse.
Transition of spatio-temporal expression of nuclear receptors in developing mouse retina suggested their roles for retinogenesis. COUP-TFs have unique expression dynamisms along with D/V axis in mouse. Their overlapped expression patterns and similarity of structure suggested that they function coordinately. Our functional assays supported this idea, and role of a network of nuclear receptors in retinogenesis will be discussed.
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