A morphogenetic EphB/EphrinB code controls hepatopancreatic duct formation

TY - JOUR

T1 - A morphogenetic EphB/EphrinB code controls hepatopancreatic duct formation

AU - Thestrup, M Ilcim

AU - Caviglia, Sara

AU - Cayuso, Jordi

AU - Heyne, Ronja L S

AU - Ahmad, Racha

AU - Hofmeister, Wolfgang

AU - Satriano, Letizia

AU - Wilkinson, David G

AU - Andersen, Jesper B

AU - Ober, Elke A

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-13149-7

DO - 10.1038/s41467-019-13149-7

M3 - Journal article

C2 - 31745086

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5220

ER -