A possible role for the high mobility group box transcription factor Tcf-4in vertebrate gut epithelial cell differentiation

The Wingless (Wg)/Wnt signaling pathway activates High Mobility Group (HMG) -box transcription factors of the T-cell Factor (Tcf)/Lymphoid Enhancer Fac tor (LEF) subfamily and mediates diverse functions in development, possibly including endoderm and gut differentiation. Determinants of tissue specifi city in the response to Wg/Wnt signaling remain unknown. We have identified Tcf-4 as the predominant Tcf/LEF factor in the developing mouse gut. Durin g fetal development, Tcf-4 mRNA expression is restricted to gut epithelium and specific regions of the brain, the thalamus and roof of the midbrain. I n adults, expression is widespread, with highest levels observed in the liv er, an endodermally derived organ, and persists in the gastrointestinal tra ct. Murine Tcf-4 has multiple RNA splice variants with consequently signifi cant heterogeneity in sequences 3' to the HMG box. Microinjection of mRNA o r plasmid DNA encoding Tcf-4 into Xenopus embryos results in ectopic expres sion of molecular markers of endoderm and differentiated gut epithelium in isolated animal cap explants. Taken together, these findings point to a pot entially important function for Tcf-4 in development of the vertebrate gast rointestinal tract.