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First published online 11 April 2007
doi: 10.1242/dev.001495

Development 134, 1873-1885 (2007)
Published by The Company of Biologists 2007
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pygopus 2 has a crucial, Wnt pathway-independent function in lens induction

Ni Song1,2,3,4, Kristopher R. Schwab5, Larry T. Patterson6, Terry Yamaguchi7, Xinhua Lin2,4, Steven S. Potter2,4 and Richard A. Lang1,2,3,4,*

1 Divisions of Pediatric Ophthalmology, Children's Hospital Research Foundation, Cincinnati, OH45229, USA.
2 Divisions of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, OH45229, USA.
3 Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, OH45229, USA.
4 Graduate Program of Molecular and Developmental Biology, College of Medicine, University of Cincinnati, Cincinnati, OH45229, USA.
5 Department of Pathology, University of Michigan, 109 Zina Pitcher Drive, Ann Arbor, MI48109, USA.
6 Division of Nephrology, Children's Hospital Research Foundation, Cincinnati, OH45229, USA.
7 Cancer and Developmental Biology Laboratory, Cell Signaling in Vertebrate Development Section, National Cancer Institute, Frederick, MD 21701-1201, USA.

* Author for correspondence (e-mail: Richard.Lang{at}cchmc.org)

Accepted 27 February 2007

Drosophila Pygopus was originally identified as a core component of the canonical Wnt signaling pathway and a transcriptional coactivator. Here we have investigated the microophthalmia that arises in mice with a germline null mutation of pygopus 2. We show that this phenotype is a consequence of defective lens development at inductive stages. Using a series of regionally limited Cre recombinase transgenes for conditional deletion of Pygo2flox, we show that Pygo2 activity in pre-placodal presumptive lens ectoderm, placodal ectoderm and ocular mesenchyme all contribute to lens development. In each case, Pygo2 is required for normal expression levels of the crucial transcription factor Pax6. Finally, we provide multiple lines of evidence that although Pygo2 can function in the Wnt pathway, its activity in lens development is Wnt pathway-independent.

Key words: Pax6, pygopus 2, Wnt, Lens induction, Mesenchyme, Neural crest, Mouse


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