Protein-O-fucosylation of co-receptors may be required for Nodal signaling in Xenopus.

Nodal-related ligands of TGF-β family play pivotal roles for mesoderm induction and body axis formation during vertebrate early embryogenesis. Nodal ligands are distinct from most other TGF-β ligands family as they require EGF-CFC factors as co-receptors for signaling, in addition to their cognate type I and type II TGF-β receptors. In amphibian Xenopus laevis embryos, five nodal-related genes (Xnr1/2/4/5/6) and two EGF-CFC genes (XCR1, XCR3) play roles in mesoderm induction and the accumulation of phosphorylated Smad2, while in mammalian embryos one Nodal gene and one EGF-CFC gene (Cripto) play roles during mesoderm induction.