Prox1 is one of the earliest markers of the murine embryonic liver territory (arrowheads in A). Previous studies in my lab demonstrated that lack of Prox1 function prevents the delamination of hepatic progenitors (a.k.a. hepatoblasts, arrowhead in B) from the gut tube and the subsequent hepatoblast colonization of the liver (C). We also showed that Prox1-deficiency severely impairs hepatocyte differentiation (D). We will use our mouse models, organ explant cultures and protocols of mouse and human iPS/ESCs directed differentiation, to unravel the mechanism that controls hepatoblast delamination and to understand how morphogenetic processes influences hepatic cell fate specification. Also, in silico, bioinformatics and conditional-deletion approaches will be used to determine the role of Prox1 in the regulatory network that establishes hepatocyte identity and function.