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L. Zhang, H.M. El-hodiri, H. Ma, X. Zhang, M. Servetnick, T.G. Wensel, M. Jamrich; Targeted Expression of the Dominant Negative FGFR-4a in the Eye Using Xrx1A Regulatory Sequences Interferes With Normal Retinal Cell Differentiation . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1610.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Rx is a paired-like homeobox gene that has been identified in several vertebrate species, and has a critical function in vertebrate eye development. Since Rx shows highly specific expression in the retinal progenitor cells, its regulatory sequences would be uniquely suited to direct gene expression into the developing retina. Fibroblast Growth Factors (FGFs) and their receptors are expressed in developing retina. The role of FGF signaling through the receptor FGFR-1 and FGFR-2 in the proliferation, survival, and differentiation of retinal cells has been investigated. However, the function of FGF receptor-4a mediated FGF signaling in retinal development has not yet been examined. The purpose of this study is to identify and characterize the regulatory sequences of the Xenopus laevis Rx1A gene, and investigate the role of FGF signaling mediated by FGFR-4a in the differentiation of retinal cell types in Xenopus laevis. Methods: Transgenic Xenopus laevis tadpoles were generated in which the dominant negative FGFR-4a (ΔFGFR-4a) coding region was linked to the newly characterized regulatory sequences of the Xrx1A gene. Immunostaining was performed to identify the retinal cell types in the eyes of transgenic tadpoles. Results: We have found that the expression of the ΔFGFR-4a in the retinal progenitor cells results in abnormal retinal development. In the transgenic Xenopus embryos expressing the ΔFGFR-4a, the normal multilayered structure is disrupted in the neural retina, and the population of photoreceptor cells is either absent or significantly reduced. Conclusions: These experiments show that FGFR-4a mediated FGF signaling in the retina is necessary for correct differentiation of retinal cell types. Furthermore, they demonstrate that constructs utilizing the Xrx1A regulatory sequences are excellent tools to study the developmental processes involved in retinal formation.
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