Cell signalling through Frizzled receptors has evolved to considerable comp
lexity within the metazoans. The Frizzled-dependent signalling cascade comp
rises several branches, whose differential activation depends on specific W
nt ligands, Frizzled receptor isoforms and the cellular context. In Xenopus
laevis embryos, the canonical beta -catenin pathway contributes to the est
ablishment of the dorsal-ventral axis(1). A different branch, referred to a
s the planar cell polarity pathway, is essential for cell polarization duri
ng elongation of the axial mesoderm by convergent extension(2). Here we dem
onstrate that a third branch of the cascade is independent of Dishevelled f
unction and involves signalling through trimeric G proteins and protein kin
ase C (PKC). During gastrulation, Frizzled-7 (Fz7)-dependent PKC signalling
controls cell-sorting behaviour in the mesoderm. Loss of zygotic Fz7 funct
ion results in the inability of involuted anterior mesoderm to separate fro
m the ectoderm, which leads to severe gastrulation defects. This result pro
vides a developmentally relevant in vivo function for the Fz/PKC pathway in
vertebrates.