The Making of the Liver: Competence in the Foregut Endoderm and Induction of Liver-Specific Genes

Abstract

The making of the vertebrate liver occurs in a two-step process, beginning with theestablishment of competence in the foregut endoderm to respond to signals fromcardiac mesoderm, followed by the induction of liver-specific gene expression. Twowinged helix transcription factors, Foxa1 and Foxa2, act in concert in hepaticspecification. In a mouse model engineered to lack both of these genes in the foregutendoderm, no liver bud is formed and expression of even the earliest knownhepatoblast markers does not occur. Furthermore, foregut endoderm derived fromdouble mutant embryos is not responsive to inductive signals in vitro. TheFoxa1/Foxa2 model is the first of a completely “liver-less mouse” and provides strongevidence for the competence model of hepatic induction.