Wnt and TGF-β signaling are required for the induction of an in vitro model of primitive streak formation using embryonic stem cells

• DOI: 10.1073/pnas.0603916103
• Publication Date: 2006-11-02T13:25:30Z
• Authors: Paul Gadue; Tara L. Huber; Patrick J. Paddison; Gordon M. Keller
• Keywords: Primitive streak; FOXA2; Nodal signaling; Germ layer

The establishment of the primitive streak and its derivative germ layers, mesoderm endoderm, are prerequisite steps in formation many tissues. To model these developmental stages vitro, an ES cell line was established that expresses CD4 from foxa2 locus addition to GFP brachyury locus. A GFP-Bry(+) population expressing variable levels CD4-Foxa2 developed upon differentiation this line. Analysis gene-expression patterns potential revealed CD4-Foxa2(hi)GFP-Bry(+) displays characteristics anterior streak, whereas CD4-Foxa2(lo)GFP-Bry(+) cells resemble posterior streak. Using model, we were able demonstrate Wnt TGF-beta/nodal/activin signaling simultaneously required for generation CD4-Foxa2(+)GFP-Bry(+) population. or low activin-induced a population, high activin resulted fate. Finally, sustained found stimulate endoderm commitment These findings early events involved germ-layer induction embryo recapitulated uncover insights into pathways endoderm.