A late requirement for Wnt and FGF signaling during activin-induced formation of foregut endoderm from mouse embryonic stem cells

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Mattias Hansson
  • ,
  • Dorthe R Olesen, Denmark
  • Janny M L Peterslund
  • ,
  • Nina Engberg
  • ,
  • Morten Østergaard Kahn
  • ,
  • Maria Karin Winzi, Denmark
  • Tino Klein
  • ,
  • Palle Serup
  • ,
  • Poul Maddox-Hyttel
  • Department of Molecular Biology
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.
Original languageEnglish
Book seriesAdvances in Developmental Biology
Volume330
Issue2
Pages (from-to)286-304
Number of pages19
ISSN1574-3349
DOIs
Publication statusPublished - 15 Jun 2009

    Research areas

  • Activins, Animals, Base Sequence, Cell Differentiation, Cells, Cultured, Chick Embryo, Embryonic Stem Cells, Endoderm, Fibroblast Growth Factors, Flow Cytometry, Fluorescent Antibody Technique, Mice, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Wnt Proteins

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