Challenges and Opportunities in Spatiotemporal Models of Mammalian Gastrulation

How cells diversify to form an embryo represents a profound interdisciplinary challenge. Decades of innovative research using model organisms have uncovered principles of lineage specification, morphogenesis, epigenetic mechanisms, and gene regulation that underlie this fundamental process. As biology enters the genomic era, marked by rapid convergence of technological and computational advances, construction of quantitative and heuristic models of development becomes increasingly feasible. In gastrulation, a founding population of equipotent stem cells rapidly diversifies in a highly canonical manner to form the basic body plan. This review discusses considerations required to establish a time-resolved model that reflects the cellular and molecular aspects involved in this process. Building on insights from recent studies and the transformative potential of evolving technologies and experimental frameworks, we discuss how to devise such a model by integrating multiple molecular modalities at the single-cell level within the spatial context as a benchmark for studying cell specification.