11-P003 Searching for the components of the Ds/Ft pathway in Drosophila and their orthologs in mouse

Specification of the mammalian left–right (L–R) axis is controlled by fluid flows in the embryonic node, a ciliated pit like structure located at the distal tip of the mouse embryo. Nodal cilia rotate so as to cause a leftward fluid flow-this has been experimentally demonstrated to control embryonic sidedness. How the embryo interprets this flow remains the subject of debate. The two cilia hypothesis argues that immotile cilia are deformed by flow, causing a Pkd2-dependent left sided Ca2+ signal. Other hypotheses argue that morphogens become asymmetrically localised in response to flow. Rikishi (rks), an ENU-derived point mutant, displays striking defects in L-R patterning that phenocopy the Pkd2 mutant. While Pkd1 interacts with Pkd2 in the kidney to produce a stress induced Ca2+ channel, Pkd1 has no role in L–R patterning. The rks mutation is in a conserved residue in a Pkd1 related gene. We therefore, propose that rks interacts with Pkd2 in L–R patterning in the node, supporting the two cilia hypothesis. However, when we examined cilia motility in Pkd2 and rks mutant embryos, we found that while Pkd2 / nodal cilia were motile, rks mutant nodal cilia were immotile. The rks and Pkd2 phenotypes are distinct from immotile cilia phenotypes, revealing a dual role for rks: in combination with Pkd2 in flow detection as well as a previously unrecognised role for Ca2+ signalling in cilia motility in the mouse node.