A morphogenetic EphB/EphrinB code controls hepatopancreatic duct formation

M. Ilcim Thestrup, Sara Caviglia, Jordi Cayuso, Ronja L. S. Heyne, Racha Ahmad, Wolfgang Hofmeister, Letizia Satriano, David G. Wilkinson, Jesper B. Andersen and Elke A. Ober ()
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M. Ilcim Thestrup: NNF Center for Stem Cell Biology (DanStem)
Sara Caviglia: NNF Center for Stem Cell Biology (DanStem)
Jordi Cayuso: Neural Development Laboratory
Ronja L. S. Heyne: NNF Center for Stem Cell Biology (DanStem)
Racha Ahmad: NNF Center for Stem Cell Biology (DanStem)
Wolfgang Hofmeister: NNF Center for Stem Cell Biology (DanStem)
Letizia Satriano: University of Copenhagen, Biotech Research and Innovation Centre
David G. Wilkinson: Neural Development Laboratory
Jesper B. Andersen: University of Copenhagen, Biotech Research and Innovation Centre
Elke A. Ober: NNF Center for Stem Cell Biology (DanStem)

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract The hepatopancreatic ductal (HPD) system connects the intrahepatic and intrapancreatic ducts to the intestine and ensures the afferent transport of the bile and pancreatic enzymes. Yet the molecular and cellular mechanisms controlling their differentiation and morphogenesis into a functional ductal system are poorly understood. Here, we characterize HPD system morphogenesis by high-resolution microscopy in zebrafish. The HPD system differentiates from a rod of unpolarized cells into mature ducts by de novo lumen formation in a dynamic multi-step process. The remodeling step from multiple nascent lumina into a single lumen requires active cell intercalation and myosin contractility. We identify key functions for EphB/EphrinB signaling in this dynamic remodeling step. Two EphrinB ligands, EphrinB1 and EphrinB2a, and two EphB receptors, EphB3b and EphB4a, control HPD morphogenesis by remodeling individual ductal compartments, and thereby coordinate the morphogenesis of this multi-compartment ductal system.

Date: 2019
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DOI: 10.1038/s41467-019-13149-7

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