Bilaterian animals are not entirely bilaterally symmetrical, with many organs and structures asymmetric on the left-right (L-R) axis. Symmetry breaking in the embryo has been investigated for decades, but its molecular control and evolutionary origins are still an active matter of debate. Now, Yiquan Wang, Guang Li and colleagues utilise amphioxus, a basal chordate which shows clear L-R asymmetry in larval structures, as a model for bilaterian and deuterostome symmetry breaking. Building on their previous work showing Hedgehog (Hh) signalling is upstream of Dand5 (the orthologue of the L-R patterning gene Cerberus), they now show that Hh signalling pathway components become progressively restricted to the right hand side of the anterior mesoderm of the embryo. Artificially increasing Hh signalling in the left side induces ectopic Dand5 expression there, whereas Dand5 expression in Hh–/– mutants is rescued upon Smoothened or Hh mRNA injection. When the Hh mRNA is injected into unfertilized eggs, the resultant Hh protein localises to where Hh signalling is normally activated at early neurula stage (that is, asymmetrically), but fails to accumulate there when cilia movement is disrupted. Indeed, loss of cilia or disruption of cilia movement disrupts asymmetric gene expression and leads to left isomerism phenotypes. Finally, Smoothened appears to promote Hh signalling in cilia via a cilia-localisation motif. This work thus puts Hh, and the motile cilia that promote its signalling, at the start of symmetry breaking in this basal chordate.
