Synthetic Biology Journal
2025, 6 (
):
669-684.
Understanding how a fertilized egg develops from a single cell into complex tissues and organs remains a central question in developmental biology. However, in mammals, especially in humans, technical and ethical constraints limit in utero investigation of the post-implantation development and ex utero culture beyond organogenesis as well. As a result, the molecular and cellular mechanisms underpinning spatiotemporal regulation during these stages remain poorly understand. This knowledge gap underscores the urgent need for high-fidelity in vitro models that not only recapitulate in vivo developmental processes but also allow for precise experimental perturbations. Recent advances in stem cell-based embryo models and organoids leverage the developmental potential and intrinsic self-organizing capabilities of pluripotent stem cells to mimic aspects of early embryonic and organ development, offering new platforms for studying those complex processes. Concurrently, synthetic biology provides powerful tools, such as programmable gene circuits, optogenetics, and engineered signaling pathways, to control gene expression, cell differentiation, intercellular communications, and tissue patterning with unprecedented precision. This review highlights recent progress in integrating synthetic biology with in vitro models to dissect and reconstitute fundamental mechanisms of embryonic development. By harnessing synthetic biology tools, researchers can now modulate specific pathways with temporal and spatial precision, enabling a deeper understanding of processes such as signal transduction dynamics, cellular adhesion networks, symmetry breaking, and the establishment of polarity. This bottom-up “build-to-learn” approach shifts the paradigm from observational to predictive developmental biology. Such innovations have collectively given rise to the emerging field of synthetic developmental biology. This field not only provides mechanistic insights into developmental events that were previously inaccessible but also opens new avenues for building artificial tissues and structures with tailored functions. We also discuss current limitations in mimicking the morphology and function of natural embryonic structures, emphasizing the need for robust evaluation systems and refined strategies to precisely control cell behavior. Finally, we explore how synthetic developmental biology can elucidate key principles of embryogenesis and accelerate future applications in regenerative medicine.
