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First published online 1 July 2009
doi: 10.1242/dev.032888

Development 136, 2567-2578 (2009)
Published by The Company of Biologists 2009
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Pax6 is essential for lens fiber cell differentiation

Ohad Shaham1, April N. Smith2, Michael L. Robinson3, Makoto M. Taketo4, Richard A. Lang2 and Ruth Ashery-Padan1,*

1 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
2 Department of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.
3 Department of Zoology, Miami University, Oxford, OH 45056, USA.
4 Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoé-cho, Sakyo, Kyoto 606-8501, Japan.

* Author for correspondence (e-mail: ruthash{at}post.tau.ac.il)

Accepted 17 May 2009

The developing ocular lens provides an excellent model system with which to study the intrinsic and extrinsic cues governing cell differentiation. Although the transcription factors Pax6 and Sox2 have been shown to be essential for lens induction, their later roles during lens fiber differentiation remain largely unknown. Using Cre/loxP mutagenesis, we somatically inactivated Pax6 and Sox2 in the developing mouse lens during differentiation of the secondary lens fibers and explored the regulatory interactions of these two intrinsic factors with the canonical Wnt pathway. Analysis of the Pax6-deficient lenses revealed a requirement for Pax6 in cell cycle exit and differentiation into lens fiber cells. In addition, Pax6 disruption led to apoptosis of lens epithelial cells. We show that Pax6 regulates the Wnt antagonist Sfrp2 in the lens, and that Sox2 expression is upregulated in the Pax6-deficient lenses. However, our study demonstrates that the failure of differentiation following loss of Pax6 is independent of β-catenin signaling or Sox2 activity. This study reveals that Pax6 is pivotal for initiation of the lens fiber differentiation program in the mammalian eye.

Key words: Pax6, Sox2, Lens, Crystallin, Wnt, β-catenin, Mouse


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© The Company of Biologists Ltd 2009