title: Brachyury cooperates with Wnt/β-catenin signalling to elicit primitive-streak-like behaviour in differentiating mouse embryonic stem cells.
abstract: BACKGROUND
  The formation of the primitive streak is the first visible sign of gastrulation, the process by which the three germ layers are formed from a single epithelium during early development. Embryonic stem cells (ESCs) provide a good system for understanding the molecular and cellular events associated with these processes. Previous work, both in embryos and in culture, has shown how converging signals from both nodal/TGFβR and Wnt/β-catenin signalling pathways specify cells to adopt a primitive-streak-like fate and direct them to undertake an epithelial-to-mesenchymal transition (EMT). However, many of these approaches have relied on genetic analyses without taking into account the temporal progression of events within single cells. In addition, it is still unclear to what extent events in the embryo are able to be reproduced in culture.
  
  
  RESULTS
  Here, we combine flow cytometry and a quantitative live single-cell imaging approach to demonstrate how the controlled differentiation of mouse ESCs towards a primitive streak fate in culture results in cells displaying many of the characteristics observed during early mouse development including transient brachyury expression, EMT and increased motility. We also find that the EMT initiates the process, and this is both fuelled and terminated by the action of brachyury, whose expression is dependent on the EMT and β-catenin activity.
  
  
  CONCLUSIONS
  As a consequence of our analysis, we propose that a major output of brachyury expression is in controlling the velocity of the cells that are transiting out of the primitive streak.
authors.forename: David A
authors.initials: DA
authors.lastname: Turner
authors.forename: Pau
authors.initials: P
authors.lastname: Rué
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Mackenzie
authors.forename: Eleanor
authors.initials: E
authors.lastname: Davies
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martinez Arias
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D004622:Embryo, Mammalian / Q000196:embryology; D053595:Embryonic Stem Cells / Q000166:cytology*; D005326:Fetal Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D054240:Primitive Streak / Q000196:embryology*; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D051176:beta Catenin; D000098908:Brachyury Protein; C495267:CTNNB1 protein, mouse