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First published online 3 May 2006
doi: 10.1242/dev.02381

Development 133, 2149-2154 (2006)
Published by The Company of Biologists 2006
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Dkk2 plays an essential role in the corneal fate of the ocular surface epithelium

Mahua Mukhopadhyay1, Marat Gorivodsky1, Svetlana Shtrom1, Alexander Grinberg1, Christoph Niehrs2, Maria I. Morasso3,* and Heiner Westphal1,*,{dagger}

1 Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
2 German Cancer Research Center, Heidelberg, Germany.
3 Developmental Skin Biology Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

{dagger} Author for correspondence (e-mail: hw{at}mail.nih.gov)

Accepted 28 March 2006

The Dkk family of secreted cysteine-rich proteins regulates Wnt/ß-catenin signaling by interacting with the Wnt co-receptor Lrp5/6. Here, we show that Dkk2-mediated repression of the Wnt/ß-catenin pathway is essential to promote differentiation of the corneal epithelial progenitor cells into a non-keratinizing stratified epithelium. Complete transformation of the corneal epithelium into a stratified epithelium that expresses epidermal-specific differentiation markers and develops appendages such as hair follicles is achieved in the absence of the Dkk2 gene function. We show that Dkk2 is a key regulator of the corneal versus epidermal fate of the ocular surface epithelium.

Key words: Mouse, Dkk2, Cornea, Epidermis, Differentiation, Wnt/ß-catenin


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