The internal organs of all vertebrates show distinct left-right (L-R) asymmetry. The earliest known event in the establishment of this asymmetry is a leftwards extracellular fluid flow at the embryonic node. This ‘nodal flow’, which is generated by the rotational movement of node cilia, activates asymmetric gene expression. But how is nodal flow detected? The two-cilia hypothesis proposes that, whereas motile cilia generate the flow, immobile node cilia detect nodal flow and respond by generating a left-sided Ca2+ signal. This signal generation is thought to be mediated by a complex consisting of the calcium channel polycystic kidney disease 2 (Pkd2) and an unknown sensor protein. In this issue, two papers further evaluate this hypothesis.
On p. 1131, Dominic Norris and colleagues identify the Pkd1-related locus Pkd1l1 as the missing Pkd2 partner and sensor protein in L-R patterning in mouse. Point mutants in either Pkd1l1 or Pkd2 fail...
