May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Negative Regulation of FGF Signaling in the Lens by Sef
Author Affiliations & Notes
  • P. J. Newitt
    Save Sight Institute & Anatomy and Histology, Bosch Institute, University of Sydney, Sydney, Australia
  • M. L. Robinson
    Department of Zoology, University of Miami, Miami, Ohio
  • J. W. McAvoy
    Save Sight Institute & Anatomy and Histology, Bosch Institute, University of Sydney, Sydney, Australia
  • F. J. Lovicu
    Save Sight Institute & Anatomy and Histology, Bosch Institute, University of Sydney, Sydney, Australia
  • Footnotes
    Commercial Relationships P.J. Newitt, None; M.L. Robinson, None; J.W. McAvoy, None; F.J. Lovicu, None.
  • Footnotes
    Support NHMRC (Australia), NIH Grant EY03177
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2004. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      P. J. Newitt, M. L. Robinson, J. W. McAvoy, F. J. Lovicu; Negative Regulation of FGF Signaling in the Lens by Sef. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2004. doi: https://doi.org/.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose:: Sef (a transmembrane protein antagonistic for FGF signalling via FGF receptors 1 & 2) is primarily expressed in the lens epithelial cells (Boros et al., 2007, SCDB). Overexpression of full length Sef in the lens of transgenic mice hinders fiber cell elongation during lens morphogenesis. The main aims of this study were to better understand the mechanism(s) underlying this process, as well as to determine which ocular factors are important for the maintenance of Sef expression in the epithelium of the intact lens.

Methods:: We characterised the progeny of transgenic lines of mice overexpressing Sef specifically in the lens, that were crossed to FGF receptor (FGFR1 & 2)-deficient lines. Moreover, we examined transgenic lines overexpressing hSef-b, a spliced isoform of Sef lacking a signal peptide sequence. Rat lens epithelial explants were also used in an attempt to identify the putative ocular factors that modulate Sef expression in vivo.

Results:: In contrast to full length Sef, overexpression of hSefb in lenses of transgenic mice did not impact on lens development. Furthermore, overexpression of full length Sef in lenses of transgenic mice deficient for FGFR1 & 2 was still able to hinder primary fiber cell elongation. These FGFR-deficient lenses were more sensitive to the effects of overexpressing Sef, displaying a more severe lens phenotype. In vitro studies also showed that aqueous but not vitreous humor was sufficient to maintain lens epithelial expression of Sef.

Conclusions:: Our study demonstrated that membrane- associated Sef is required to influence FGF signalling in the lens. Moreover, this is the first report of Sef influencing FGFR activity, independent of FGFR1 and FGFR2. Our in vitro studies also indicate that aqueous-derived factors are required for the maintenance of Sef expression in the lens epithelium.

Keywords: development • signal transduction • transgenics/knock-outs 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×