Prostaglandin E2 Regulates Liver versus Pancreas Cell-Fate Decisions and Endodermal Outgrowth

Summary The liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here we describe prostaglandin E 2 (PGE 2 ) as a regulator of endodermal fate specification during development. Modulating PGE 2 activity has opposing effects on liver versus pancreas specification in zebrafish embryos as well as mouse endodermal progenitors. The PGE 2 synthetic enzyme cox2a and receptor ep2a are patterned such that cells closest to PGE 2 synthesis acquire a liver fate, whereas more distant cells acquire a pancreas fate. PGE 2 interacts with the bmp2b pathway to regulate fate specification. At later stages of development, PGE 2 acting via the ep4a receptor promotes outgrowth of both the liver and pancreas. PGE 2 remains important for adult organ growth, as it modulates liver regeneration. This work provides in vivo evidence that PGE 2 may act as a morphogen to regulate cell-fate decisions and outgrowth of the embryonic endodermal anlagen.