RRC ID 76477
Author Tanaka Y, Morozumi A, Hirokawa N.
Title Nodal flow transfers polycystin to determine mouse left-right asymmetry.
Journal Dev Cell
Abstract 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 overexpression significantly augments cellular Nodal sensitivity, we propose that leftward transfer of polycystin-containing fibrous strands determines left-right asymmetry in developing embryos.
Published 2023-6-27
DOI 10.1016/j.devcel.2023.06.002
PII S1534-5807(23)00275-7
PMID 37413993
MeSH Animals Body Patterning Cilia / metabolism Gene Expression Regulation, Developmental Hedgehog Proteins* / metabolism Mice Nodal Protein / metabolism Signal Transduction TRPP Cation Channels* / genetics TRPP Cation Channels* / metabolism Transforming Growth Factor beta / metabolism
IF 10.092
Human and Animal Cells 293T(RCB2202) NIH3T3-3-4(RCB1862)
DNA material NIA 15K Mouse cDNA Clone H3025A11 (MCH010011)