BMP4 plays a key role in left-right patterning in chick embryos by maintaining sonic hedgehog asymmetry

In chick embryos, the first signs of left-right asymmetry are detected in Hensen's node, essentially by left-sided Sonic Hedgehog (Shh) expression. After a gap of several hours, SHH induces polarized gene activities in the left paraxial mesoderm. We show that during this time period, BMP4 signaling is necessary and sufficient to maintain Shh asymmetry within the node. SHH and BMP4 proteins negatively regulate each other's transcription, resulting in a strict complementarity between these two gene patterns on each side of the node. Noggin, present in the midline at this stage, limits BMP4 spreading. Moreover, BMP4 is downstream to Activin signals and controls Fgf8. Thus, early BMP4 signaling coordinates left and right pathways in Hensen's node.