Neurturin-GFRalpha2 signaling controls liver bud migration along the ductus venosus in the chick embryo.
During chick liver development, the liver bud arises from the foregut, invaginates into the septum transversum, and elongates along and envelops the ductus venosus. However, the mechanism of liver bud migration is only poorly understood. Here, we demonstrate that a GDNF family ligand involved in neuronal outgrowth and migration, neurturin (NRTN), and its receptor, GFRalpha2, are essential for liver bud migration. In the chick embryo, we found that GFRalpha2 was expressed in the liver bud and that NRTN was expressed in the endothelial cells of the ductus venosus. Inhibition of GFRalpha2 signaling suppressed liver bud elongation along the ductus venous without affecting cell proliferation and apoptosis. Moreover, ectopic expression of NRTN perturbed the directional migration along the ductus venosus, leading to splitting or ectopic branching of the liver. We showed that liver buds selectively migrated toward an NRTN-soaked bead in vitro. These data represent a new model for liver bud migration: NRTN secreted from endothelial cells functions as a chemoattractant to direct the migration of the GFRalpha2-expressing liver bud in early liver development.
Tatsumi
Norifumi
N
Division of Pattern Formation, Department of Organogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Miki
Rika
R
Katsu
Kenjiro
K
Yokouchi
Yuji
Y
D000818:Animals; D001775:Blood Circulation; D002465:Cell Movement; D002630:Chemotactic Factors / Q000502:physiology; D002642:Chick Embryo; D042783:Endothelial Cells; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D009024:Morphogenesis; D051101:Neurturin / Q000502:physiology*; D038081:Organogenesis; D015398:Signal Transduction
D002630:Chemotactic Factors; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051101:Neurturin