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Open Access Highly Accessed Research article

A transcriptional response to Wnt protein in human embryonic carcinoma cells

Jennifer Willert13, Mirjam Epping14, Jonathan R Pollack25, Patrick O Brown2 and Roel Nusse1*

Author Affiliations

1 Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305 USA

2 Department of Biochemistry, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305 USA

3 Children's Hospital, San Diego, USA

4 Netherlands Cancer Institute, Amsterdam, The Netherlands

5 Dept of Pathology, Stanford University, CA, USA

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BMC Developmental Biology 2002, 2:8  doi:10.1186/1471-213X-2-8

Published: 2 July 2002

Abstract

Background

Wnt signaling is implicated in many developmental decisions, including stem cell control, as well as in cancer. There are relatively few target genes known of the Wnt pathway.

Results

We have identified target genes of Wnt signaling using microarray technology and human embryonic carcinoma cells stimulated with active Wnt protein. The ~50 genes upregulated early after Wnt addition include the previously known Wnt targets Cyclin D1, MYC, ID2 and βTRCP. The newly identified targets, which include MSX1, MSX2, Nucleophosmin, Follistatin, TLE/Groucho, Ubc4/5E2, CBP/P300, Frizzled and REST/NRSF, have important implications for understanding the roles of Wnts in development and cancer. The protein synthesis inhibitor cycloheximide blocks induction by Wnt, consistent with a requirement for newly synthesized β-catenin protein prior to target gene activation. The promoters of nearly all the target genes we identified have putative TCF binding sites, and we show that the TCF binding site is required for induction of Follistatin. Several of the target genes have a cooperative response to a combination of Wnt and BMP.

Conclusions

Wnt signaling activates genes that promote stem cell fate and inhibit cellular differentiation and regulates a remarkable number of genes involved in its own signaling system.