How a simple free-floating blastocyst develops into a more complex embryo that initiates gastrulation to build a body has remained a key question to which an answer is largely unknown. This is because this transition happens when embryo implants within the body of the mother and therefor becomes hidden from observations and manipulations. We have recently developed a culture system that for the first time allows us to film this transition as it happens in living embryos, outside the body of the mother. This has revealed that pluripotent cells of the blastocyst self-organise into a rosette-like structure from which the future body will emerge. Moreover, we can instruct ES cells to mimic this process when culture in the same 3D system. The aim of this PhD is to discover the mechanism, on cellular and molecular level, of this self-organisation using both embryos and ES cells developing in vitro. Specifically: (1) in order to understand how morphogenesis happens, ES cells carrying fluorescent protein tagged transgenes, that mark different cell types, will be introduced into blastocysts and their fate will be followed by the time-lapse fluorescent microscopy and 4D analyses. (2) In order to understand the role of Wnt, BMP and Nodal signalling pathways at this developmental transition, mutant ES cells in such pathways will be introduced into blastocysts to follow the consequences for morphogenesis and gastrulation. This PhD project will allow to establish the thus far hidden sequence of events leading to gastrulation and the mechanisms of this key developmental transition.
- Morris et al Nature Communication 2012 (Zernicka-Goetz group)
- Morris et al Cell Reports 2013 (Zernicka-Goetz group)
- Bedzhov and Zernicka-Goetz, Cell 2014 (Zernicka-Goetz group)