Document Detail

A late requirement for Wnt and FGF signaling during activin-induced formation of foregut endoderm from mouse embryonic stem cells.
MedLine Citation:
PMID:  19358838     Owner:  NLM     Status:  MEDLINE    
Here we examine how BMP, Wnt, and FGF signaling modulate activin-induced mesendodermal differentiation of mouse ES cells grown under defined conditions in adherent monoculture. We monitor ES cells containing reporter genes for markers of primitive streak (PS) and its progeny and extend previous findings on the ability of increasing concentrations of activin to progressively induce more ES cell progeny to anterior PS and endodermal fates. We find that the number of Sox17- and Gsc-expressing cells increases with increasing activin concentration while the highest number of T-expressing cells is found at the lowest activin concentration. The expression of Gsc and other anterior markers induced by activin is prevented by treatment with BMP4, which induces T expression and subsequent mesodermal development. We show that canonical Wnt signaling is required only during late stages of activin-induced development of Sox17-expressing endodermal cells. Furthermore, Dkk1 treatment is less effective in reducing development of Sox17(+) endodermal cells in adherent culture than in aggregate culture and appears to inhibit nodal-mediated induction of Sox17(+) cells more effectively than activin-mediated induction. Notably, activin induction of Gsc-GFP(+) cells appears refractory to inhibition of canonical Wnt signaling but shows a dependence on early as well as late FGF signaling. Additionally, we find a late dependence on FGF signaling during induction of Sox17(+) cells by activin while BMP4-induced T expression requires FGF signaling in adherent but not aggregate culture. Lastly, we demonstrate that activin-induced definitive endoderm derived from mouse ES cells can incorporate into the developing foregut endoderm in vivo and adopt a mostly anterior foregut character after further culture in vitro.
Mattias Hansson; Dorthe R Olesen; Janny M L Peterslund; Nina Engberg; Morten Kahn; Maria Winzi; Tino Klein; Poul Maddox-Hyttel; Palle Serup
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-04-07
Journal Detail:
Title:  Developmental biology     Volume:  330     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-25     Completed Date:  2009-06-12     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  286-304     Citation Subset:  IM    
Department of Developmental Biology, Hagedorn Research Institute, Niels Steensens Vej 6, DK-2820 Gentofte, Denmark.
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MeSH Terms
Activins / pharmacology*
Base Sequence
Cell Differentiation
Cells, Cultured
Chick Embryo
Embryonic Stem Cells / cytology*
Endoderm / cytology,  drug effects*
Fibroblast Growth Factors / metabolism*
Flow Cytometry
Fluorescent Antibody Technique
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction*
Wnt Proteins / metabolism*
Grant Support
Reg. No./Substance:
0/RNA, Small Interfering; 0/Wnt Proteins; 104625-48-1/Activins; 62031-54-3/Fibroblast Growth Factors

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