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

The liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here we describe prostaglandin E2 (PGE2) as a regulator of endodermal fate specification during development. Modulating PGE2 activity has opposing effects on liver versus pancreas specification in zebrafish embryos as well as mouse endodermal progenitors. The PGE2 synthetic enzyme cox2a and receptor ep2a are patterned such that cells closest to PGE2 synthesis acquire a liver fate, whereas more distant cells acquire a pancreas fate. PGE2 interacts with the bmp2b pathway to regulate fate specification. At later stages of development, PGE2 acting via the ep4a receptor promotes outgrowth of both the liver and pancreas. PGE2 remains important for adult organ growth, as it modulates liver regeneration. This work provides in vivo evidence that PGE2 may act as a morphogen to regulate cell-fate decisions and outgrowth of the embryonic endodermal anlagen. •PGE2 acts as a morphogen to regulate liver versus pancreas specification of endoderm•Expression of PGE2 pathway genes is patterned to regulate endoderm specification•PGE2 interacts with bmp2b signaling to promote a liver fate over a pancreas fate•PGE2 promotes organ growth later in development and liver regeneration in adults Prostaglandins have long been recognized to modulate processes such as vasoregulation and inflammation. Here, Nissim et al. find evidence for prostaglandin E2 in regulating the specification of endoderm into liver or pancreas in the context of embryonic development.