A dual action of XTcf-3 in body axis formation

Abstract

The role of the TCF family of transcriptional regulators in primary axis formation is addressed by studying the mechanisms of action of XTcf-3 in Xenophus laevis embryos. The early events of primary axis induction involve activation through the WNT signaling pathway. As a result of activation of the pathway the cytoplasmic level of ß-catenin increases at the future dorsal side of the early cleavage stage embryo. Around the 16-32 cell stage, ß-catenin becomes apparent in the nuclei. The presence of nuclear ß-catenin causes several hours later the activation of specific target genes, like e.g. XSiamois. Since ß-catenin does not contain a DNA binding region, DNA binding proteins must mediate this transactivation. Ectopic expression of ß-catenin causes activation of dorsal genes and results in the induction and differentiation of a secondary axis. (See introduction). Three different homologs of the Tcf/Lef family of transcription factors have been cloned in Xenopus laevis, XTcf-3, XLef-1 and XTcf-4 (Chapter 3). Only transcripts of XTcf-3 are present maternally and therefore likely to be involved in axis specification. As described in chapters 2 and 4, during axis induction in Xenopus laevis embryos, XTcf-3 can act both as an activator as well as a repressor of transcription.