) The authors claim that Nodal/Vg0 heterodimers mediate Nodal signaling. This statement requires at least direct prove that such heterodimers bind to nodal receptors and, ideally, that they mediate receptor activation. This could be shown by IP experiments showing binding of both Cyc and Vg0 to phosphorylated Nodal receptors.  0\) The authors show that Vg0 binds to Cyc and Sqt in vivo by colocalization of tagged versions of these ligands in the extracellular space ([Figure 0](#fig0){ref-type="fig"}). These colocalizations should be quantified to show what fraction of extracellular Vg0 is bound to Nodal ligands and vice-versa.  Also, in [Figure 0: a](#fig0){ref-type="fig"}) Co-expression of cyc and Vg0-GFP changes Vg0 localization from completely intracellular to completely extracellular. Same for co-expression with Sqt ([Figure 0B](#fig0){ref-type="fig"}). Is this true? Or is it due to differences in Image exposure? A quantification of this should be provided. Also it would be interesting to know if the fraction of extracellular Vg0 depends on the amount of Nodal ligand provided.  b\) The distribution of Sqt-dsRED in [Figure 0D](#fig0){ref-type="fig"} looks very different from that of Sqt-GFP in [Figure 0](#fig0){ref-type="fig"} and from that of Vg-0 in the presence of Sqt in [Figure 0B](#fig0){ref-type="fig"}. Why is this so?  0\) If Nodal signaling is mediated by heterodimers of Nodal and Vg0, the extent of Nodal signaling should depend on their stoichiometry. It would be interesting to overexpress different relative amounts of Vg0 and Nodal ligand in Vg0 mutant and analyse Nodal signaling activation (via Smad0 nuclear localization for instance).  0\) The authors provide a simple theoretical model to show how the presence of maternally contributed Vg0 speeds up Nodal signaling upon production of Nodal ligands. I feel this is not particularly revealing: the idea that one component of a pathway being readily available speeds up signaling does not require modeling to be put forward. Moreover, the model is based on parameters measured or inferred for the Nodal ligands, which do not necessarily hold true for Vg0.  