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Dev Cell. 2014 Feb 24;28(4):423-37. doi: 10.1016/j.devcel.2014.01.006. Epub 2014 Feb 13.

Prostaglandin E2 regulates liver versus pancreas cell-fate decisions and endodermal outgrowth.

Author information

1
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.
2
Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
3
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
4
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.
5
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.

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.

PMID:
24530296
PMCID:
PMC4006117
DOI:
10.1016/j.devcel.2014.01.006
[Indexed for MEDLINE]
Free PMC Article
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