Signaling regulation during gastrulation: Insights from mouse embryos and in vitro systems

Gastrulation is the process whereby cells exit pluripotency and concomitantly acquire and pattern distinct cell fates. This is driven by the convergence of WNT, BMP, Nodal and FGF signals, which are tightly spatially and temporally controlled, resulting in regional and stage-specific signaling environments. The combination, level and duration of signals that a cell is exposed to, according its position within the embryo and the developmental time window, dictates the fate it will adopt. The key pathways driving gastrulation exhibit complex interactions, which are difficult to disentangle in vivo due to the complexity of manipulating multiple signals in parallel with high spatiotemporal resolution. Thus, our current understanding of the signaling dynamics regulating gastrulation is limited. In vitro stem cell models have been established, which undergo organized cellular differentiation and patterning. These provide amenable, simplified, deconstructed and scalable models of gastrulation. While the foundation of our understanding of gastrulation stems from experiments in embryos, in vitro systems are now beginning to reveal the intricate details of signaling regulation. Here we discuss the current state of knowledge of the role, regulation and dynamic interaction of signaling pathways that drive mouse gastrulation.