June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
A Role for the Fat/Dachsous System in Lens Development
Author Affiliations & Notes
  • John McAvoy
    Save Sight Institute, University of Sydney, Sydney, NSW, Australia
  • Yuki Sugiyama
    Save Sight Institute, University of Sydney, Sydney, NSW, Australia
  • Christopher Harris
    Save Sight Institute, University of Sydney, Sydney, NSW, Australia
  • Lucy Dawes
    Save Sight Institute, University of Sydney, Sydney, NSW, Australia
  • Elizabeth Shelley
    Save Sight Institute, University of Sydney, Sydney, NSW, Australia
  • Caroline Badouel
    Samuel Lunenfeld Research Institute, Toronto, ON, Canada
  • Helen McNeill
    Samuel Lunenfeld Research Institute, Toronto, ON, Canada
  • Frank Lovicu
    Anatomy & Histology, University of Sydney, Sydney, NSW, Australia
  • Footnotes
    Commercial Relationships John McAvoy, None; Yuki Sugiyama, None; Christopher Harris, None; Lucy Dawes, None; Elizabeth Shelley, None; Caroline Badouel, None; Helen McNeill, None; Frank Lovicu, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 480. doi:
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    • Get Citation

      John McAvoy, Yuki Sugiyama, Christopher Harris, Lucy Dawes, Elizabeth Shelley, Caroline Badouel, Helen McNeill, Frank Lovicu; A Role for the Fat/Dachsous System in Lens Development. Invest. Ophthalmol. Vis. Sci. 2013;54(15):480.

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

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Abstract

Purpose: Recent studies show that planar cell polarity (PCP) operates in the lens. PCP is generated through the activity of two groups of proteins, the Wnt-Frizzled/PCP system and the Fat/Dachsous (Dchs) system. Whilst some progress has been made in understanding the role of Wnt-Frizzled/PCP signalling, nothing is known about the Fat/Dchs system in the lens. The purpose of this study was to initiate investigations into the distribution of Fat and Dchs family members in the lens and determine if they have a role in its development.

Methods: In situ hybridization and immunofluorescence were used to study expression of members of the Fat and Dchs families during lens morphogenesis. To assess Fat/Dchs function, Fat1 and Fat4 gene knockout (KO) mice were examined.

Results: Both Fat 1 and Fat 4 are strongly expressed in most cells of the lens pit. At later stages both Fats are restricted to the anterior cells of the lens vesicle and subsequently the lens epithelium; neither Fat is detected in lens fibers. Dchs1 has a more ubiquitous distribution and is present in both epithelial and fiber cells; it is particularly strongly expressed in the transition zone at the lens equator. Fat1-/-;Fat4+/+, Fat1-/-;Fat4+/- and Fat1-/-;Fat4-/- mice have smaller eyes than normal. This defect is most pronounced in the double KO mouse. In all cases the lens is also smaller with the main defect being in the epithelium. Loss of apical-basal polarity is evident and cells no longer form a regularly-packed monolayer. Small plaques of cells are also evident with some cells showing reactivity for the epithelial mesenchymal transition marker, alpha-smooth muscle actin.

Conclusions: Results from this study show prominent expression of components of the Fat/Dchs system in the lens. Initial studies of Fat KO mice clearly show a role for this pathway in formation and maintenance of the lens epithelial phenotype.

Keywords: 497 development • 543 growth factors/growth factor receptors • 500 differentiation  
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