PUBLICATION

Crucial role of vHNF1 in vertebrate hepatic specification

Authors
Lokmane, L., Haumaitre, C., Garcia-Villalba, P., Anselme, I., Schneider-Maunoury, S., and Cereghini, S.
ID
ZDB-PUB-080722-19
Date
2008
Source
Development (Cambridge, England)   135(16): 2777-2786 (Journal)
Registered Authors
Anselme, Isabelle, Schneider-Maunoury, Sylvie
Keywords
Liver specification, vHNF1 (HNF1β, TCF2), Mouse, Zebrafish
MeSH Terms
  • Animals
  • Cell Differentiation/physiology
  • Endoderm/embryology*
  • Endoderm/physiology
  • Female
  • Fibroblast Growth Factors/physiology
  • Hepatocyte Nuclear Factor 1-beta/genetics
  • Hepatocyte Nuclear Factor 1-beta/physiology*
  • Hepatocytes/cytology*
  • Hepatocytes/physiology
  • Liver/cytology
  • Liver/embryology*
  • Liver/physiology
  • Male
  • Mesoderm/embryology*
  • Mesoderm/physiology
  • Mice
  • Species Specificity
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed
18635606 Full text @ Development
Abstract
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping