The septum transversum mesenchyme induces gall bladder development

The liver, gall bladder, and ventral pancreas are formed from the posterior region of the ventral foregut. After hepatic induction, Sox17+/Pdx1+ pancreatobiliary common progenitor cells differentiate into Sox17+/Pdx1- gall bladder progenitors and Sox17-/Pdx1+ ventral pancreatic progenitors, but the cell-extrinsic signals that regulate this differentiation process are unknown. This study shows that the septum transversum mesenchyme (STM) grows in the posterior direction after E8.5, becoming adjacent to the presumptive gall bladder region, to induce gall bladder development. In this induction process, STM-derived BMP4 induces differentiation from common progenitor cells adjacent to the STM into gall bladder progenitor cells, by maintaining Sox17 expression and suppressing Pdx1 expression. Furthermore, the STM suppresses ectopic activation of the liver program in the posterior region of the ventral foregut following hepatic induction through an Fgf10/Fgfr2b/Sox9 signaling pathway. Thus, the STM plays pivotal roles in gall bladder development by both inductive and suppressive effects.