Gut endoderm is involved in the transfer of left-right asymmetry from the node to the lateral plate mesoderm in the mouse embryo

Left-right (LR) determination during embryogenesis is critical for the correct positioning of the various visceral organs, such as the lungs and the heart. In establishing LR asymmetry in the mouse, the initial LR signal that is determined in the ciliated embryonic node is transferred to the lateral plate mesoderm (LPM). The cellular and molecular mechanisms for this signal transfer have not been well characterized. Here, we studied the role of endoderm cells in this process by analyzing mouse Sox17 null mutant embryos as a model that develops endoderm-specific defects. Sox17 mutant embryos showed no expression or significantly reduced expression of LR asymmetric genes in the left LPM. A series of experiments revealed the importance of intercellular communication through gap junctions in endoderm cells for LR signal transfer from the node. We also found that SOX17 function is essential not only to form complete epithelial structures that express CX43 and localize connexin proteins on the cell membrane but also to turn off Nodal gene expression in differentiating endoderm cells through a Nodal endoderm-specific enhancer.