Nodal signaling induces the midline barrier by activating Nodal expression in the lateral plate

The transcription factor Foxh1 mediates Nodal signaling. The role of Foxh1 in left-right (LR) patterning was examined with mutant mice that lack this protein in lateral plate mesoderm (LPM). The mutant mice failed to express Nodal, Lefty2 and Pitx2 on the left side during embryogenesis and exhibited right isomerism. Ectopic introduction of Nodal into right LPM, by transplantation of left LPM or by electroporation of a Nodal vector, induced Nodal expression in wild-type embryos but not in the mutant. Ectopic Nodal expression in right LPM also induced Lefty1 expression in the floor plate. Nodal signaling thus initiates asymmetric Nodal expression in LPM and induces Lefty1 at the midline. Monitoring of Nodal activity in wild-type and Foxh1 mutant embryos suggested that Nodal activity travels from the node to left LPM, and from left LPM to the midline.