The first five years of the Wnt targetome

The canonical Writ pathway controls cell differentiation, proliferation and apoptosis by regulating the expression of a high number of target genes. The first target gene of the Wnt pathway was discovered nearly 20 years ago, when analysing gene expression patterns in the Drosophila embryo. Since the year 2002 entire transcriptomes have been screened by microarray analysis in order to identify genes, which are differentially expressed in cells with activated Wnt pathway. Recently, novel genome-based screening methods have been developed, which are less error-prone and independent from RNA. The exemplified methods STAGE (Sequence Tag Analysis Of Genomic Enrichment), ChIP-PET (chromatin immunoprecipitation with paired-end ditag), ChIP-Seq (ChIP followed by direct sequencing) and the bioinformatics approach EEL (Enhancer Element Locator) will be introduced shortly. The high number of potential target genes and regulated functions left questions unanswered, for instance how the Wnt pathway controls such a high number of genes and how it is able to regulate so many different cellular functions. In order to answer these questions we ordered the genes of the published Wnt target screenings according to their functions, and summarized the pathways, which are regulated by the Wnt pathway. This review focuses on the totality of Wnt target genes, the Wnt targetome, which is the clue to understand the manifold roles of the Wnt pathway within the cellular context. (C) 2007 Elsevier Inc. All rights reserved.