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Homeodomain protein Pitx3 maintains the mitotic activity of lens epithelial cells

Ho, Hsin-Yi, Chang, Kuo-Hsuan, Nichols, Jennifer and Li, Meng 2009. Homeodomain protein Pitx3 maintains the mitotic activity of lens epithelial cells. Mechanisms of Development 126 (1-2) , pp. 18-29. 10.1016/j.mod.2008.10.007

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Abstract

Pitx3 is a bicoid like homeobox transcription factor of which deficiency in mice is linked with the aphakia phenotype. Mutation in human PITX3 gene is associated with autosomal dominant cataract with variable anterior segment mesenchymal dysgenesis. However, the molecular events causing the morphological changes in aphakia remains unknown. In this study we investigated the behaviour of GFP tagged Pitx3 null embryonic stem cells in chimeric lens, as well as the molecular features of the Pitx3-deficient lens of homozygous Pitx3 knockout mice. We show that the lack of colonisation of Pitx3-deficient ES cell derivatives in Pitx3 wild-type ↔ Pitx3 null chimeric lens was due to the depletion of the epithelial cells in lens epithelium manifested by aberrant cell cycle exit and precocious onset of fibre cell differentiation of the Pitx3 null cells at the lens vesicle stage. This was demonstrated by the early activation of the cell cycle inhibitors p27Kip1 and p57Kip2, and the expression of β-and γ-crystallins. These defects are at least partially attributed to the loss of FoxE3 and misexpression of Prox1 in the lens vesicle epithelial cells. Thus, Pitx3 is essential to maintain lens epithelial phenotype and prevent inappropriate fibre cell differentiation during lens development.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
Subjects: Q Science > Q Science (General)
Uncontrolled Keywords: Pitx3; Homeodomain transcription factor; Lens epithelium; Fibre cell; Differentiation.
Publisher: Elsevier
ISSN: 0925-4773
Last Modified: 04 Jun 2017 06:38
URI: http://orca.cf.ac.uk/id/eprint/63091

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