The vertebrate transcription factors TCF/LEF (T cell factor/lymphoid enhancer binding protein) were initially identified by their differential expression and DNA binding during T cell and B cell differentiation. dTCF was cloned in Drosophila to determine the in vivo function of TCF. Experiments using two-hybrid in yeast and ectopic expression in Xenopus suggested that TCF/LEF family members interact with Armadillo/-catenin to transduce Wingless/WNT signals during development. In addition, elevated levels of TCF/-catenin are observed in human colon cancer and melanoma. My goal is to determine how TCF functions in vivo, how it is regulated during development and to develop it as a model for studying colon and other cancers. We collaborated in the cloning of the Drosophila TCF homolog dTCF. We mapped the gene to the base of the fourth chromosome and identified mutations that partially or fully inactivate dTCF. We demonstrated that both in vitro and in vivo dTCF interacts with Armadillo/-catenin to transduce Wingless/WNT signaling. We are now focusing on the regulation and functioning of dTCF. We are generating antibodies to the Drosophila protein and inducing more mutations. These will be used in second-site genetic screens to look for additional interacting proteins and to identify direct down-stream targets of Wingless signaling.
