EphrinB1/EphB3b coordinate bidirectional epithelial-mesenchymal interactions controlling liver morphogenesis and laterality
journal contributionposted on 2020-07-15, 10:48 authored by Jordi Cayuso, Aliaksandr Dzementsei, Johanna C Fischer, Gopal Karemore, Sara Caviglia, Josefin Bartholdson, Gavin J Wright, Elke A Ober
Positioning organs in the body often requires the movement of multiple tissues, yet the molecular and cellular mechanisms coordinating such movements are largely unknown. Here, we show that bidirectional signaling between EphrinB1 and EphB3b coordinates the movements of the hepatic endoderm and adjacent lateral plate mesoderm (LPM), resulting in asymmetric positioning of the zebrafish liver. EphrinB1 in hepatoblasts regulates directional migration and mediates interactions with the LPM, where EphB3b controls polarity and movement of the LPM. EphB3b in the LPM concomitantly repels hepatoblasts to move leftward into the liver bud. Cellular protrusions controlled by Eph/Ephrin signaling mediate hepatoblast motility and long-distance cell-cell contacts with the LPM beyond immediate tissue interfaces. Mechanistically, intracellular EphrinB1 domains mediate EphB3b-independent hepatoblast extension formation, while EpB3b interactions cause their destabilization. We propose that bidirectional short- and long-distance cell interactions between epithelial and mesenchyme-like tissues coordinate liver bud formation and laterality via cell repulsion.
EphB3EphrinB1bidirectionallateral plate mesodermlivermigrationmorphogenesisprotrusionrepulsionzebrafishAnimalsBody PatterningCell MovementCell ShapeEphrin-B1Ephrin-B3EpitheliumFunctional LateralityLiverMesodermMorphogenesisPseudopodiaReceptors, Eph FamilyZebrafishZebrafish ProteinsWilkinson, D FC001217Elgar FC001075BRF-ackSB-ackDevelopmental Biology06 Biological Sciences11 Medical and Health Sciences