Leftward transfer of a chemosensory polycystin initiates left-dominant calcium signaling for lateralized embryonic development

Abstract

SummaryLeft-dominant [Ca2+]ielevation on the margin of ventral node furnishes the initial laterality signaling in mouse embryos. It depends on nodal flow, FGFR signaling, and PKD1L1-containing polycystin channels, of which interrelationship is still missing. Here we show that PKD1L1 protein is predominantly accumulated on the left margin of the nodal pit and serves as a chemosensory channel for Nodal-mediated [Ca2+]ielevation. PKD1L1/PKD2 overexpression augmented the Nodal sensitivity of fibroblasts. We detected PKD1L1-containing fragile meshwork of fibrous strands using KikGR-PKD1L1 knockin mice, especially when the extraembryonic membrane was preserved. The portion of meshwork bridging over nodal crown cells significantly lateralized to the left. This bridge was formed by a leftward flow of PKD1L1-containing fibrous strands, which can be suppressed by the FGFR inhibitor SU5402 that antagonized the [Ca2+]ielevation as well. These data provide evidence for a leftward transfer of chemosensory PKD1L1 polycystin channel, as a readout mechanism of nodal flow.