EphrinB1/EphB3b coordinate bidirectional epithelial-mesenchymal interactions controlling liver morphogenesis and laterality Jordi Cayuso Aliaksandr Dzementsei Johanna C Fischer Gopal Karemore Sara Caviglia Josefin Bartholdson Gavin J Wright Elke A Ober 10779/crick.12619736.v1 https://crick.figshare.com/articles/journal_contribution/EphrinB1_EphB3b_coordinate_bidirectional_epithelial-mesenchymal_interactions_controlling_liver_morphogenesis_and_laterality/12619736 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. 2020-07-15 10:48:18 EphB3 EphrinB1 bidirectional lateral plate mesoderm liver migration morphogenesis protrusion repulsion zebrafish Animals Body Patterning Cell Movement Cell Shape Ephrin-B1 Ephrin-B3 Epithelium Functional Laterality Liver Mesoderm Morphogenesis Pseudopodia Receptors, Eph Family Zebrafish Zebrafish Proteins Wilkinson, D FC001217 Elgar FC001075 BRF-ack SB-ack Developmental Biology 06 Biological Sciences 11 Medical and Health Sciences