Pygopus - a core component of the canonical Wnt-signalling pathway - plays a crucial role in development and disease. Its essential transcriptional co-activator activity is mediated through its interaction with β-catenin,Tcf, Bcl9 and Hyrax. In Xenopus, Pygopus 2 (Pygo2) orthologues regulate the expression of eye markers. Surprisingly though, it has been suggested that this activity operates independently of the Wnt pathway. Richard Lang and co-workers() now show that lens development in mice depends on Pygo2-mediated regulation of the transcription factor Pax6. They further show that Pygo2 function, in this setting, is Wnt-independent. By conditionally deleting Pygo2 in certain tissues in mice where it is normally expressed - the ocular mesenchyme and the presumptive lens ectoderm (PLE) - these researchers show that Pax6 expression is reduced in the PLE and a small lens subsequently develops. Interestingly, they find that Pygo1 is dispensable for lens development. Future work should uncover the pathway in which Pygo2 operates during lens development and reveal whether Pygo2 has other Wnt-independent roles.
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