Nodal flow transfers polycystin to determine mouse left-right asymmetry

Left-dominant [Ca2+]i elevation on the left margin of the ventral node furnishes the initial laterality of mouse embryos. It depends on extracellular leftward fluid flow (nodal flow), fibroblast growth factor receptor (FGFR)/ sonic hedgehog (Shh) signaling, and the PKD1L1 polycystin subunit, of which interrelationship is still elusive. Here, we show that leftward nodal flow directs PKD1L1-containing fibrous strands and facilitates Nodal mediated [Ca2+]i elevation on the left margin. We generate KikGR-PKD1L1 knockin mice in order to monitor protein dynamics with a photoconvertible fluorescence protein tag. By imaging those embryos, we have identified fragile meshwork being gradually transferred leftward involving pleiomorphic extracellular events. A portion of the meshwork finally bridges over the left nodal crown cells in an FGFR/Shh-dependent manner. As PKD1L1 N-term is predominantly associated with Nodal on the left margin and that PKD1L1/PKD2 over expression significantly augments cellular Nodal sensitivity, we propose that leftward transfer of polycystincontaining fibrous strands determines left-right asymmetry in developing embryos.

Automated summary

Left-dominant [Ca2+]i elevation at the left margin of the ventral node plays a crucial role in determining the initial laterality of mouse embryos. This process is dependent on extracellular leftward fluid flow, fibroblast growth factor receptor (FGFR)/ sonic hedgehog (Shh) signaling, and the PKD1L1 polycystin subunit, although their interrelationships are not fully understood. By studying KikGR-PKD1L1 knockin mice, researchers have discovered that leftward nodal flow guides PKD1L1-containing fibrous strands and facilitates Nodal mediated [Ca2+]i elevation at the left margin. They propose that the leftward transfer of polycystin-containing fibrous strands determines the left-right asymmetry in developing embryos.