The liver and ventral pancreas are thought to develop from a common pool of multipotent progenitors. Although a number of studies have identified factors required for either pancreas or liver specification, factors that are distinctly required to specify the entire hepatopancreas system have not yet been reported. Now, Joseph Lancman and co-workers uncover a common genetic program, involving hnf1ba and wnt2bb, that specifies progenitors of the liver, ventral pancreas, gall bladder and associated ducts in zebrafish (). By characterising a new hnf1ba hypomorphic mutant that phenocopies pancreatic defects found in people with HNF1B monogenic diabetes, the researchers show that hnf1ba regulates pancreas specification and β-cell numbers. Furthermore, they report, the combination of Hnf1ba partial loss with conditional loss of Wnt signalling reveals that these pathways synergize during a narrow developmental window to specify hepatopancreas progenitors; Hnf1ba acts to generate a Wnt permissive domain in the foregut that in turn adopts a hepatopancreatic fate. In summary, these findings highlight a new model for hepatopancreas specification and provide important insights into pancreas and β-cell development.
