Vertebrate development and patterning require Nodal signalling. However, the upstream inducers of Nodal expression and the relative contributions of Nodal ligands from embryonic, extraembryonic and maternal sources to embryogenesis are unclear. Now, Benjamin Feldman and co-workers show that non-embryonic sources of Nodal-related ligands, activated in part by the transcription factor Mxtx2, account for the spectrum of zebrafish early Nodal signalling events (p. 787). They report that Mxtx2 activates and is required for the expression of nodal-related 2 (ndr2) in the yolk syncytial layer, an extraembryonic tissue, thus identifying a novel upstream component of Nodal signalling. They further demonstrate that the co-disruption of extraembryonic ndr2, extraembryonic nodal-related 1 (ndr1) and maternal ndr1 recapitulates Nodal mutant phenotypes: embryos show a loss of endoderm and anterior mesoderm specification. Based on their findings, the authors propose that endoderm and anterior mesoderm specification during zebrafish development is executed by a failsafe mechanism involving the combined action of non-embryonic Nodal-related ligands, and that this mechanism may be relevant to higher vertebrates.