title: Prostaglandin E2 regulates liver versus pancreas cell-fate decisions and endodermal outgrowth.
abstract: 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.
authors: Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors: Sahar
authors: S
authors: Nissim
authors: Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: Richard I
authors: RI
authors: Sherwood
authors: Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: Julia
authors: J
authors: Wucherpfennig
authors: Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: Diane
authors: D
authors: Saunders
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors: James M
authors: JM
authors: Harris
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors: Virginie
authors: V
authors: Esain
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors: Kelli J
authors: KJ
authors: Carroll
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors: Gregory M
authors: GM
authors: Frechette
authors: Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: Andrew J
authors: AJ
authors: Kim
authors: Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: Katie L
authors: KL
authors: Hwang
authors: Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: Claire C
authors: CC
authors: Cutting
authors: Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: Susanna
authors: S
authors: Elledge
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: tnorth@bidmc.harvard.edu.
authors: Trista E
authors: TE
authors: North
authors: Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: wgoessling@partners.org.
authors: Wolfram
authors: W
authors: Goessling
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D015232:Dinoprostone / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D038081:Organogenesis; D010179:Pancreas / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D029961:Zebrafish Proteins; C405936:bmp2b protein, zebrafish; D015232:Dinoprostone