Establishment of the left-right (LR) body axis is a crucial step in embryogenesis. In mouse embryos, a leftward flow of fluid in the node establishes an initial LR signal, which is transferred to the lateral plate mesoderm (LPM) where it triggers the gene expression program responsible for LR asymmetry. But how is the LR signal transferred to the LPM? On p. 2426, Yukio Saijoh and co-workers test the hypothesis that endoderm (which lies next to the node and covers the LPM) is involved in this process. The researchers report that expression of LR asymmetric genes in the left LPM is greatly reduced or absent in most mouse embryos null for the Sox17 transcription factor, which exhibit endoderm-specific defects. Interestingly, membrane localization of gap junction connexin proteins is impaired and intercellular transport between endoderm cells is disrupted in Sox17–/– endoderm. Together, these results suggest that endoderm cells, possibly via gap junction communication, play an essential role in the transfer of LR signals during mouse LR axis establishment.