The key factors involved in vertebrate embryonic endoderm formation include the Nodal ligands, Mix-like paired homeodomain transcription factors, Gata transcription factors and Sox17 proteins. Although the relationships between these proteins are commonly described using a linear model - in which Nodal proteins regulate Mixer and Gata, which then regulate Sox17 to turn on endoderm target genes - Zorn and colleagues (p. 1955) have now used microarrays and loss-of-function experiments in Xenopus to show that the story is more complicated. They identified 300 transcripts enriched in the gastrula endoderm, which included most of the known endoderm regulators and several hundred uncharacterised sequences. Surprisingly, the linear model of endoderm formation only predicted 10% of the endoderm transcriptome. The authors also identified several novel epistatic relationships, including autoregulatory loops between Sox, Gata, Bix and Xnr4. They also found that,contrary to common understanding, much of Mixer activity is independent of Sox17. This first global analysis of vertebrate endoderm formation will be a vital reference point for future experiments into this complex molecular network.