The Onecut transcription factors HNF-6/OC-1 and OC-2 regulate early liver expansion by controlling hepatoblast migration.
Liver development in mammals is initiated by the formation of a hepatic bud from the ventral foregut endoderm. The hepatic cells then proliferate and invade the septum transversum mesenchyme, and further differentiate to give rise to hepatocytes and biliary cells. By analyzing mice that are knockout for the transcription factors Hepatocyte Nuclear Factor-6 (HNF-6)/Onecut-1 (OC-1) and OC-2, we show here that these factors redundantly stimulate the degradation of the basal lamina surrounding the liver bud and promote hepatoblast migration in the septum transversum. Gene expression analysis indicates that HNF-6 and OC-2 belong to a gene network comprising E-cadherin, thrombospondin-4 and osteopontin, which regulates liver bud expansion by controlling hepatoblast migration and adhesion. This network operating at the onset of liver development contains candidate genes for investigation of liver carcinogenesis.
Margagliotti
Sabrina
S
Université Catholique de Louvain, Christian de Duve Institute of Cellular Pathology, Avenue Hippocrate 75/7529, B-1200 Brussels, Belgium.
Clotman
Frédéric
F
Pierreux
Christophe E
CE
Beaudry
Jean-Bernard
JB
Jacquemin
Patrick
P
Rousseau
Guy G
GG
Lemaigre
Frédéric P
FP
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051559:Hepatocyte Nuclear Factor 6 / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000033:anatomy & histology / Q000196:embryology* / Q000254:growth & development; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
D051559:Hepatocyte Nuclear Factor 6; D018398:Homeodomain Proteins; C487964:ONECUT2 protein, mouse; C496606:Onecut1 protein, mouse; C506896:Spp1 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D053495:Osteopontin