A transcriptional response to Wnt protein in human embryonic carcinoma cells.
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.
Willert
Jennifer
J
Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305 USA. jennifer.willert@cox.net
Epping
Mirjam
M
Pollack
Jonathan R
JR
Brown
Patrick O
PO
Nusse
Roel
R
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D029721:Drosophila Proteins / Q000378:metabolism; D051157:Frizzled Receptors; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D005796:Genes / Q000235:genetics; D006801:Humans; D007739:L Cells / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D018243:Teratocarcinoma / Q000235:genetics* / Q000473:pathology; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D029721:Drosophila Proteins; D051157:Frizzled Receptors; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C101703:fz2 protein, Drosophila