The EGF-CFC protein one-eyed pinhead is essential for nodal signaling

The zebrafish EGF-CFC gene one-eyed pinhead (oep) is required zygotically f or the formation of the ventral neuroectoderm, endoderm, and prechordal pla te. Here we report that embryos lacking both maternal and zygotic Oep activ ity are defective in germ layer formation, organizer development, and the p ositioning of the anterior-posterior axis. An identical phenotype is displa yed by double mutants for the nodal-related genes squint and cyclops. Mutat ions in oep eliminate the response to Squint and Cyclops overexpression but are suppressed by expression of Activin and activated forms of the type I receptor ActRIB and Smad2. Expression of the murine EGF-CFC gene cripto res cues oep mutants. These results suggest a conserved role for EGF-CFC protei ns as essential extracellular cofactors for Nodal signaling during vertebra te development.