| A late requirement for Wnt and FGF signaling during activin-induced formation of foregut endoderm from mouse embryonic stem cells. | |
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MedLine Citation:
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PMID: 19358838 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-04-07 |
Journal Detail:
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Title: Developmental biology Volume: 330 ISSN: 1095-564X ISO Abbreviation: Dev. Biol. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-05-25 Completed Date: 2009-06-12 Revised Date: 2013-06-02 |
Medline Journal Info:
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Nlm Unique ID: 0372762 Medline TA: Dev Biol Country: United States |
Other Details:
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Languages: eng Pagination: 286-304 Citation Subset: IM |
Affiliation:
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Department of Developmental Biology, Hagedorn Research Institute, Niels Steensens Vej 6, DK-2820 Gentofte, Denmark. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Activins
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pharmacology* Animals 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 Mice RNA, Small Interfering Reverse Transcriptase Polymerase Chain Reaction Signal Transduction* Wnt Proteins / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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U19 DK072495-04/DK/NIDDK NIH HHS; U19-DK04-017/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Small Interfering; 0/Wnt Proteins; 104625-48-1/Activins; 62031-54-3/Fibroblast Growth Factors |
| Comments/Corrections | |
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