Wnt Signaling Through Different Transcription Factors

Abstract

The Wnt signaling pathway regulates various processes during development. In Xenopus , Wnt signaling components encoded by maternal mRNAs establish the dorsal embryonic axis very early in development. However, after the onset of zygotic transcription, Xwnt-8 promotes ventral and lateral mesoderm development and restricts dorsal mesoderm development. Roël et al. demonstrated that the mechanism whereby Wnt signaling elicits distinct responses at different embryonic stages depends on differential expression of two transcription factors, XTcf-3 and XLef-1, downstream of the Wnt pathway. By injecting dominant-negative mutant forms of XTcf-3 and XLef-1 that could not bind β-catenin into various blastomeres in Xenopus embryos, the authors confirmed that Xtcf-3 was necessary for dorsal axis formation. They also showed that XLef-1 was required for zygotic, ventrolateral mesoderm-promoting development and for expression of tissue-specific genes regulated by Xwnt-8. The dominant-negative XLef-1 mutant rescued embryos from ectopic Xwnt-8 signaling but not from ectopic maternal Wnt signaling, whereas the Xtcf-3 mutant had the reverse effect. Antisense morpholino oligonucleotides against XLef-1 injected into blastomeres inhibited development and interfered with expression of the marker gene XmyoD similarly to the constitutively repressing XLef-1 mutant. Co-expressing human Lef-1, which is not inhibited by the antisense morpholino, rescued XmyoD expression, confirming that this phenotype results from loss of the XLef-1 gene product. These results suggest that the same β-catenin-dependent Wnt signaling pathway mediates both dorsal and ventrolateral development and that differential expression of the two transcription factors leads to tissue-specific responses to Wnt signaling. G. Roël, F. S. Hamilton, Y. Gent, A. A. Bain, O. Destree, S. Hoppler, Lef-1 and Tcf-3 transcription factors mediate tissue-specific Wnt signaling during Xenopus development. Curr. Biol. 12 , 1941-1945 (2002). [Online Journal]