Crucial role of vHNF1 in vertebrate hepatic specification.
Mouse liver induction occurs via the acquisition of ventral endoderm competence to respond to inductive signals from adjacent mesoderm, followed by hepatic specification. Little is known about the regulatory circuit involved in these processes. Through the analysis of vHnf1 (Hnf1b)-deficient embryos, generated by tetraploid embryo complementation, we demonstrate that lack of vHNF1 leads to defective hepatic bud formation and abnormal gut regionalization. Thickening of the ventral hepatic endoderm and expression of known hepatic genes do not occur. At earlier stages, hepatic specification of vHnf1-/- ventral endoderm is disrupted. More importantly, mutant ventral endoderm cultured in vitro loses its responsiveness to inductive FGF signals and fails to induce the hepatic-specification genes albumin and transthyretin. Analysis of liver induction in zebrafish indicates a conserved role of vHNF1 in vertebrates. Our results reveal the crucial role of vHNF1 at the earliest steps of liver induction: the acquisition of endoderm competence and the hepatic specification.
Lokmane
Ludmilla
L
Centre National de la Recherche Scientifique, UMR7622 Biologie du Developpement, 9 quai St. Bernard Bât. C, 75005 Paris, France.
Haumaitre
Cécile
C
Garcia-Villalba
Pilar
P
Anselme
Isabelle
I
Schneider-Maunoury
Sylvie
S
Cereghini
Silvia
S
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004707:Endoderm / Q000196:embryology* / Q000502:physiology; D005260:Female; D005346:Fibroblast Growth Factors / Q000502:physiology; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D008297:Male; D008648:Mesoderm / Q000196:embryology* / Q000502:physiology; D051379:Mice; D013045:Species Specificity; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
C496496:Hnf1b protein, mouse; D029961:Zebrafish Proteins; C496498:hnf1ba protein, zebrafish; D051539:Hepatocyte Nuclear Factor 1-beta; D005346:Fibroblast Growth Factors