Nodal flow transfers polycystin to determine mouse left-right asymmetry

• Published in: Developmental cell 2023-08, Vol.58 (16), p.1447-1461.e6
• Main Authors: Tanaka, Yosuke, Morozumi, Ai, Hirokawa, Nobutaka
• Format: Article
• Language: English
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2023.06.002

Left-dominant [Ca ] 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 [Ca ] 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 overexpression significantly augments cellular Nodal sensitivity, we propose that leftward transfer of polycystin-containing fibrous strands determines left-right asymmetry in developing embryos.