Where There's a Wnt, There's a Way

Abstract

Although Xenopus dorsoventral axis specification involves intracellular components of the canonical Wnt signaling pathway such as β-catenin, the mechanism through which axis specification is activated--or even whether it is initiated by an extracellular signal--has been unclear (see Jessen and Solnica-Krezel). Maternal Wnt11 mRNA is present in Xenopus oocytes, leading Tao et al. to investigate its role in initiating dorsalization, even though Wnt11 is generally thought to activate noncanonical Wnt signaling pathways rather than acting through β-catenin. Wnt11 mRNA injected into full-grown oocytes caused dorsalization of the embryo together with increased expression of Wnt target genes, whereas depletion of maternal Wnt11 mRNA led to ventralization and reduced expression of Wnt target genes. The effects of Wnt11 injection were blocked by β-catenin depletion, whereas the effects of Wnt11 depletion were rescued by injection of β-catenin mRNA. Depletion of maternal mRNA encoding the glycosyl transferase Exostosin, which modifies heparan sulfate proteoglycans (HSPGs), thereby enabling them to interact with extracellular Wnt, led to embryo ventralization and reduced expression of Wnt target genes, effects that were partially rescued by injection of β-catenin mRNA. Depletion of maternally derived FRL1 (an EGF-CFC protein) also caused ventralization together with reduced expression of Wnt target genes, again partially rescued by injection of β-catenin mRNA. Tagged Wnt11 and tagged FRL1 mRNAs injected into separate blastomeres coimmunoprecipitated, which indicates that these two proteins interacted even when derived from different cells. Thus, maternally derived Wnt11 appears to initiate Xenopus dorsalization through the canonical Wnt signaling pathway by acting extracellularly through a mechanism that involves HSPGs and FRL1. Q. Tao, C. Yokota, H. Puck, M. Kofron, B. Birsoy, D. Yan, M. Asashima, C. C. Wylie, X. Lin, J. Heasman, Maternal Wnt11 activates the canonical Wnt signaling pathway required for axis formation in Xenopus embryos. Cell 120 , 857-871 (2005). [Online Journal] J. R. Jessen, L. Solnica-Krezel, Axis formation: β-catenin catches a Wnt. Cell 120 , 736-737 (2005). [Online Journal]