A morphogenetic EphB/EphrinB code controls hepatopancreatic duct formation.

Autor: Thestrup MI; University of Copenhagen, NNF Center for Stem Cell Biology (DanStem), Blegdamsvej 3B, 2200, Copenhagen N, Denmark., Caviglia S; University of Copenhagen, NNF Center for Stem Cell Biology (DanStem), Blegdamsvej 3B, 2200, Copenhagen N, Denmark., Cayuso J; The Francis Crick Institute, Neural Development Laboratory, 1 Midland Road, London, NW1 1AT, UK., Heyne RLS; University of Copenhagen, NNF Center for Stem Cell Biology (DanStem), Blegdamsvej 3B, 2200, Copenhagen N, Denmark., Ahmad R; University of Copenhagen, NNF Center for Stem Cell Biology (DanStem), Blegdamsvej 3B, 2200, Copenhagen N, Denmark., Hofmeister W; University of Copenhagen, NNF Center for Stem Cell Biology (DanStem), Blegdamsvej 3B, 2200, Copenhagen N, Denmark.; Odense University Hospital, Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Sdr. Boulevard 29, 5000, Odense C, Denmark.; University of Southern Denmark, Department of Cardiovascular and Renal Research, Winsloewparken 21, 5000, Odense C, Denmark., Satriano L; University of Copenhagen, Biotech Research and Innovation Centre, Copenhagen, Denmark., Wilkinson DG; The Francis Crick Institute, Neural Development Laboratory, 1 Midland Road, London, NW1 1AT, UK., Andersen JB; University of Copenhagen, Biotech Research and Innovation Centre, Copenhagen, Denmark., Ober EA; University of Copenhagen, NNF Center for Stem Cell Biology (DanStem), Blegdamsvej 3B, 2200, Copenhagen N, Denmark. elke.ober@sund.ku.dk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Nov 19; Vol. 10 (1), pp. 5220. Date of Electronic Publication: 2019 Nov 19.
DOI: 10.1038/s41467-019-13149-7
Abstrakt: 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.
Databáze: MEDLINE