The Initiation of Liver Development Is Dependent on Foxa Transcription Factors

Nature. 2005 Jun 16;435(7044):944-7. doi: 10.1038/nature03649.

Abstract

The specification of the vertebrate liver is thought to occur in a two-step process, beginning with the establishment of competence within the foregut endoderm for responding to organ-specific signals, followed by the induction of liver-specific genes. On the basis of expression and in vitro studies, it has been proposed that the Foxa transcription factors establish competence by opening compacted chromatin structures within liver-specific target genes. Here we show that Foxa1 and Foxa2 (forkhead box proteins A1 and A2) are required in concert for hepatic specification in mouse. In embryos deficient for both genes in the foregut endoderm, no liver bud is evident and expression of the hepatoblast marker alpha-fetoprotein (Afp) is lost. Furthermore, Foxa1/Foxa2-deficient endoderm cultured in the presence of exogenous fibroblast growth factor 2 (FGF2) fails to initiate expression of the liver markers albumin and transthyretin. Thus, Foxa1 and Foxa2 are required for the establishment of competence within the foregut endoderm and the onset of hepatogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fibroblast Growth Factor 2 / pharmacology
  • Gene Deletion
  • Gene Expression Regulation, Developmental / drug effects
  • Hepatocyte Nuclear Factor 3-alpha
  • Hepatocyte Nuclear Factor 3-beta
  • Hepatocyte Nuclear Factor 3-gamma
  • Liver / drug effects
  • Liver / embryology*
  • Liver / metabolism*
  • Mice
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Foxa1 protein, mouse
  • Foxa2 protein, mouse
  • Foxa3 protein, mouse
  • Hepatocyte Nuclear Factor 3-alpha
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Fibroblast Growth Factor 2
  • Hepatocyte Nuclear Factor 3-gamma
  • Hepatocyte Nuclear Factor 3-beta