April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Conditional Knock-out β-catenin Disrupts Mouse Fetal Eyelid Morphogenesis
Author Affiliations & Notes
  • Yujin Zhang
    Ophthalmology, University of Cincinnati School of Med, Cincinnati, Ohio
  • Winston W-Y Kao, Sr.
    Ophthalmology, University of Cincinnati School of Med, Cincinnati, Ohio
  • Chia-Yang Liu, Sr.
    Ophthalmology, University of Cincinnati School of Med, Cincinnati, Ohio
  • Footnotes
    Commercial Relationships  Yujin Zhang, None; Winston W-Y Kao, Sr., None; Chia-Yang Liu, Sr., None
  • Footnotes
    Support  RO1-12486, EY13755, Research to Prevent Blindness, Ohio Lions Eye Research Foundation
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2093. doi:
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    • Get Citation

      Yujin Zhang, Winston W-Y Kao, Sr., Chia-Yang Liu, Sr.; Conditional Knock-out β-catenin Disrupts Mouse Fetal Eyelid Morphogenesis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2093.

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

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Abstract

Purpose: : Wnt signaling plays pivotal roles in tissue morphogenesis. In this study, attmepts were made to examine the role of Wnt/β-catenin pathway in eyelid morphogenesis.

Methods: : RT-PCR and immunofluoresecne staining were employed to determine the expression of Wnts and cellular localization of Ctnnb1 in eyelid during embryonic development. The driver Kera-rtTA (KR), tet-O-Cre (TC) and β-catenin flox (Ctnnb1f/f) mice were crossed to obtain triple transgenic mice KR/TC/ Ctnnbf/f in which Ctnnb1 was ablated by feeding pregnant dams with Dox-chow commenced at the beginning of mating (E0) continued to various gestation stages e.g., E14.5, E15.5, E16.5 and postnatal day 1 when embryos and neonates were collected. The specimens were then subjected to histology and immunohistochemistry examination.

Results: : Wnt ligands including Wnt3, Wnt5a, Wnt8a, Wnt9a, Wnt9b, Wnt11 and Wnt16 were expressed by eyelid mesenchymal cells as detected by RT-PCR. Immunofluorescence staining indicated that there was a translocation of Ctnnb 1 from plasmic membrane at E13.5 to nuclei at E15.5. The ablation of β-catenin in eyelid mesenchymal cells caused anomaly of the formation of bilateral concaved eyelids at birth. Histological examinations showed that eyelid epithelium of both wild-type and β-catenin lof-mutant (lost of function) mice began to migrate at E14.5. However, the concurrent growth of eyelid stroma and subsequent eyelid closure were disrupted in β-catenin lof mutant, which normally take place at E16.5. Lof mutants also had thinner corneal stroma than that of wild type mice. It was noteworthy that number of BrdU-labeled eyelid mesenchymal cells in lof mutant is 5-fold less than that of wild type, while TUNEL assay did not show any noticeable difference. Immunohistochemistry showed that there was a upregulation of phospho-p38 but phospho-ERK was not affected in mesenchymal cells of lof mutant at E15.5.

Conclusions: : These findings suggested that the eyelid malformation caused by ablation of Ctnnb1 may be due to reduced proliferation and/or perturbed migration of periocular mesenchymal cell of neural crest origin. Canonical Wnt/β-catenin signaling in periocular mesenchymal cells plays a pivotal role for the eyelid morphogenesis during mouse embryonic development.

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