May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Targeted Expression of the Dominant Negative FGFR-4a in the Eye Using Xrx1A Regulatory Sequences Interferes With Normal Retinal Cell Differentiation
Author Affiliations & Notes
  • L. Zhang
    Program in Developmental Biology, Baylor College of Medicine, Houston, TX, United States
  • H.M. El-hodiri
    Division of Molecular and Human Genetics, Children’s Research Institute, Columbus, OH, United States
  • H. Ma
    Mcb, Harvard University, Cambridge, MA, United States
  • X. Zhang
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, United States
  • M. Servetnick
    Department of Biology, Ithaca College, Ithaca, NY, United States
  • T.G. Wensel
    Department of Biology, Ithaca College, Ithaca, NY, United States
  • M. Jamrich
    Departments of Molec and Cellular Biology and Molecullar and Human Genetics, Baylor College of Medicine, Houston, TX, United States
  • Footnotes
    Commercial Relationships  L. Zhang, None; H.M. El-hodiri, None; H. Ma, None; X. Zhang, None; M. Servetnick, None; T.G. Wensel, None; M. Jamrich, None.
  • Footnotes
    Support  NIH-NEI grant EY12505 to MJ
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1610. doi:
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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)

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Abstract

Abstract: : 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.

Keywords: retinal development • gene/expression • transgenics/knock-outs 
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