Brachyury cooperates with Wnt/β-Catenin signalling to elicit Primitive Streak like behaviour in differentiating mouse ES cells.

Citations Over Time

Abstract

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 to understand 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 as to what extent events in the embryo are able to be reproduced in culture. Here, we combine flow-cytometry and a quantitative live single-cell imaging approach to demonstrate how the controlled differentiation of mouse ESCs (mESCs) 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 Bra, whose expression is dependent on the EMT and β-Catenin activity. 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.

Related Papers

• → Staging of ovine embryos and expression of the T-box genes Brachyury and Eomesodermin around gastrulation(2004)51 cited
• → Brachyury is expressed in gastrulating bovine embryos well ahead of implantation(2001)46 cited
• → Low proliferative and high migratory activity in the area ofBrachyuryexpressing mesoderm progenitor cells in the gastrulating rabbit embryo(2002)68 cited
• → Comparison of anterior-posterior development in the porcine versus chicken embryo, using goosecoid expression as a marker(2001)8 cited
• → Differential expression ofcSmad1 andcSmad5 in the primitive streak during chick embryo gastrulation(2000)4 cited