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 betaTRCP. 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 beta-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.