Role of metalloproteinases at the onset of liver development.
At the onset of liver development, the hepatic precursor cells, namely, the hepatoblasts, derive from the ventral foregut endoderm and form a bud surrounded by a basement membrane (BM). To initiate liver growth, the hepatoblasts migrate across the BM and invade the neighboring septum transversum mesenchyme. In the present study, carried out in the mouse embryo, we searched for effectors involved in this process and we examined the role of matrix metalloproteinases (MMPs). We found expression of a broad range of MMPs, among which MMP-2 was predominantly expressed in the septum transversum and MMP-14 in the hepatoblasts. Using a new liver explant culture system we showed that inhibition of MMP activity represses migration of the hepatoblasts. We conclude that MMPs are required to initiate expansion of the liver during development and that our culture system provides a new model to study hepatoblast migration.
Margagliotti
Sabrina
S
Hormone and Metabolic Research Unit, Université Catholique de Louvain, de Duve Institute, 1200 Brussels, Belgium.
Clotman
Frédéric
F
Pierreux
Christophe E
CE
Lemoine
Pascale
P
Rousseau
Guy G
GG
Henriet
Patrick
P
Lemaigre
Frédéric P
FP
D000818:Animals; D001485:Basement Membrane / Q000196:embryology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000201:enzymology*; D053511:Matrix Metalloproteinase 14 / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D038081:Organogenesis / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology
D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14