The EGF-CFC Protein One-Eyed Pinhead Is Essential for Nodal Signaling

TLDR

The zebrafish EGF‑CFC gene one‑eyed pinhead (oep) is required zygotically for ventral neuroectoderm, endoderm, and prechordal plate formation. Loss of both maternal and zygotic Oep activity disrupts germ layer formation, organizer development, and anterior‑posterior axis positioning, mirroring squint/cyclops double mutants, abolishes response to Squint/Cyclops overexpression, but is rescued by Activin, ActRIB, Smad2, or murine cripto, indicating that EGF‑CFC proteins are essential extracellular cofactors for Nodal signaling in vertebrate development.

Abstract

The zebrafish EGF-CFC gene one-eyed pinhead (oep) is required zygotically for the formation of the ventral neuroectoderm, endoderm, and prechordal plate. Here we report that embryos lacking both maternal and zygotic Oep activity are defective in germ layer formation, organizer development, and the positioning of the anterior-posterior axis. An identical phenotype is displayed by double mutants for the nodal-related genes squint and cyclops. Mutations 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 rescues oep mutants. These results suggest a conserved role for EGF-CFC proteins as essential extracellular cofactors for Nodal signaling during vertebrate development.