PhD defence E. (Emiel) van Genderen

Below is a brief summary of the dissertation: 

We investigated how the developing mouse embryo synchronizes cell state transitions with morphogenesis during peri- to early post-implantation. During this phase, the epiblast transitions from naïve to primed pluripotency while forming a rosette-like structure that opens to form the egg cylinder.
To understand how epiblast morphogenesis and differentiation are coordinated, we first examined the regulation of pluripotency transitions. WNT and LIF maintain naïve pluripotency, while FGF/MEK signaling promotes progression to the primed state. Notably, WNT must be downregulated before MEK can induce differentiation, suggesting that WNT either blocks MEK activity or that an intermediate, MEK-responsive state exists.
We identified a distinct pluripotent state at the rosette stage, marked by co-expression of naïve markers and the primed marker OTX2. Due to its resemblance to the in vivo rosette-stage embryo, we termed this state rosette pluripotency. We show that WNT and MEK act sequentially to regulate entry to and exit from this state, and that their combined inhibition enables capture of rosette-like stem cells in vitro.
Using rosette-like stem cells and in vitro morphogenesis models, we show that it is not the cell state transitions but the shared upstream signals that coordinate morphogenesis and differentiation. WNT and MEK regulate both processes via independent modules, enabling synchronized yet adaptable development.
In conclusion, we identified a novel pluripotent state, it's signaling regulation, and show how shared signals can independently govern morphogenesis and cell state transitions. This modular control supports robust, synchronized development within and across tissues and allows compensation when coordination is impaired.