A crucial early step in establishing the dorsoventral polarity in Xenopus embryos is the dorsal accumulation of β-catenin, a component of the canonical WNT pathway. It has previously been thought that this process does not involve WNTs, but is regulated by an unidentified intracellular signal with dorsalizing activity. A new study shows that maternal WNT11 is the initial signal that, together with other extracellular factors, activates the canonical pathway in fertilized eggs.

Previous studies that manipulated Wnt11 expression in early embryos did not show any defects in axis formation. Tao and colleagues conjectured that the time window that is important for establishing polarity occurs shortly after fertilization and, therefore, might have been missed in these studies. They injected Wnt11 mRNA into oocytes before fertilization took place and found that this caused dorsalization — a process that depended on β-catenin activity and that was associated with increased expression of WNT target genes. By contrast, depleting Wnt11 expression in oocytes led to a reduction in dorsoanterior embryonic structures, which could be rescued by dorsal injection of β-catenin mRNA.

Activation of WNT pathways usually requires interaction of WNTs with specific extracellular cofactors. The authors show that a Xenopus EGF–CFC protein, fibroblast growth factor receptor ligand 1 (FRL1), and heparan sulphate proteoglycans (HSPGs) are two such cofactors for WNT11 in the axial initiation pathway. When either FRL1 or Exostosin (an enzyme that is required for the synthesis of HSPGs) was removed from oocytes, the resulting embryos had phenotypes that mimicked WNT11 depletion. This could be reversed by overexpressing β-catenin.

As the role of WNTs in pattern formation is evolutionarily conserved, it will be interesting to determine whether maternal WNTs are also important for axial initiation in other animal groups.