A dynamic expression survey identifies transcription factors relevant in mouse digestive tract development.

Tissue-restricted transcription factors (TFs), which confer specialized cellular properties, are usually identified through sequence homology or cis-element analysis of lineage-specific genes; conventional modes of mRNA profiling often fail to report non-abundant TF transcripts. We evaluated the dynamic expression during mouse gut organogenesis of 1381 transcripts, covering nearly every known and predicted TF, and documented the expression of approximately 1000 TF genes in gastrointestinal development. Despite distinctive structures and functions, the stomach and intestine exhibit limited differences in TF genes.

Insights into developmental mechanisms and cancers in the mammalian intestine derived from serial analysis of gene expression and study of the hepatoma-derived growth factor (HDGF).

The vertebrate intestine is a model for investigating inductive cellular interactions and the roles of epithelial stem cells in tissue regeneration, and for understanding parallels between development and cancer. We have used serial analysis of gene expression to measure transcript levels across stages in mouse intestine development. The data (http://genome.

Small-molecule antagonists of the oncogenic Tcf/beta-catenin protein complex.

Key molecular lesions in colorectal and other cancers cause beta-catenin-dependent transactivation of T cell factor (Tcf)-dependent genes. Disruption of this signal represents an opportunity for rational cancer therapy. To identify compounds that inhibit association between Tcf4 and beta-catenin, we screened libraries of natural compounds in a high-throughput assay for immunoenzymatic detection of the protein-protein interaction.

Characterization of a novel mammalian Groucho isoform and its role in transcriptional regulation.

The Wnt/beta-catenin/Tcf pathway serves important functions in embryonic development and is constitutively activated in human colorectal cancer. The nuclear output of Wnt signaling is mediated by a complex between DNA-binding proteins of the TCF family and the transcriptional coactivator beta-catenin. Groucho proteins act to repress transcriptional activation by beta-catenin-Tcf complexes, probably by interacting directly with Tcf transcription factors.