Genetic Interaction of PGE2 and Wnt Signaling Regulates Developmental Specification of Stem Cells and Regeneration | Zendy

Wolfram Goessling | Zendy; Trista E. North | Zendy; Sabine Loewer | Zendy; Allegra M. Lord | Zendy; Sang Lee | Zendy; Cristi L. Stoick-Cooper | Zendy; Gilbert Weidinger | Zendy; Mark Puder | Zendy; George Q. Daley | Zendy; Randall T. Moon | Zendy; Leonard I. Zon | Zendy

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Genetic Interaction of PGE2 and Wnt Signaling Regulates Developmental Specification of Stem Cells and Regeneration

Author(s) -

Wolfram Goessling,

Trista E. North,

Sabine Loewer,

Allegra M. Lord,

Sang Lee,

Cristi L. Stoick-Cooper,

Gilbert Weidinger,

Mark Puder,

George Q. Daley,

Randall T. Moon,

Leonard I. Zon

Publication year - 2009

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2009.01.015

Subject(s) - wnt signaling pathway , biology , microbiology and biotechnology , stem cell , zebrafish , hematopoietic stem cell , haematopoiesis , progenitor cell , regeneration (biology) , signal transduction , genetics , gene

Interactions between developmental signaling pathways govern the formation and function of stem cells. Prostaglandin (PG) E2 regulates vertebrate hematopoietic stem cells (HSC). Similarly, the Wnt signaling pathway controls HSC self-renewal and bone marrow repopulation. Here, we show that wnt reporter activity in zebrafish HSCs is responsive to PGE2 modulation, demonstrating a direct interaction in vivo. Inhibition of PGE2 synthesis blocked wnt-induced alterations in HSC formation. PGE2 modified the wnt signaling cascade at the level of beta-catenin degradation through cAMP/PKA-mediated stabilizing phosphorylation events. The PGE2/Wnt interaction regulated murine stem and progenitor populations in vitro in hematopoietic ES cell assays and in vivo following transplantation. The relationship between PGE2 and Wnt was also conserved during regeneration of other organ systems. Our work provides in vivo evidence that Wnt activation in stem cells requires PGE2, and suggests the PGE2/Wnt interaction is a master regulator of vertebrate regeneration and recovery.

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