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Proc Natl Acad Sci U S A. 2004 May 25;101(21):8017-21. Epub 2004 May 17.

Anteriorization of neural fate by inhibitor of beta-catenin and T cell factor (ICAT), a negative regulator of Wnt signaling.

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Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.


Inhibitor of beta-catenin and T cell factor (ICAT) inhibits Wnt signaling by interfering with the interaction between beta-catenin and T cell factor. Here we show that ICAT(-/-) embryos exhibit malformation of the forebrain and craniofacial bones and lack the kidney. Analysis of the neuronal differentiation of embryonic stem cells revealed that Wnt3a redirects the fate of neural progenitors to a posterior character, whereas ICAT induces forebrain cells by inhibiting Wnt signaling. Furthermore, ICAT(-/-) embryonic stem cells were found to differentiate into neuronal cells possessing a posterior character. These results suggest that ICAT plays an important role in the anteriorization of neural cells by inhibiting the posteriorizing activity of Wnt signaling.

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