A metabolic view of gastrulation: Coordinating signalling, epigenetics and morphogenesis

Gastrulation is the morphogenetic process by which the single-layered pluripotent epiblast is reorganised into the three germ layers and the basic body plan is established. While the metabolic state of pluripotent stem cells is well characterised, the metabolic remodelling that coincides with germ layer specification is less well understood. Emerging evidence suggests that metabolism functions as more than a passive housekeeping process and instead acts as a dynamic regulator of cell state during these developmental transitions. Here, we review recent work that implicates a role for metabolic pathways in regulating cell fate and morphogenesis during gastrulation. In particular, glucose metabolism appears to serve as a critical regulatory layer, modulating morphogen signalling to promote the emergence and function of mesodermal and endodermal populations. We also discuss the role of the tricarboxylic acid cycle and one-carbon metabolism in epigenetic remodelling and highlight the role of lipid metabolism in coupling the biophysical properties of membranes to cellular identity and morphogenetic movements. A current challenge is to distinguish in which situations metabolic shifts act as instructive drivers or permissive gatekeepers of development. Technological advances in spatial metabolomics, biosensors, and optogenetics are now facilitating the visualisation and manipulation of metabolic activity, paving the way for a mechanistic understanding of how metabolism shapes cell fate and behaviour during gastrulation.