gastruloid

Gastruloids are three-dimensional, in vitro aggregates derived from pluripotent stem cells that model key aspects of early embryonic gastrulation. They recapitulate some of the spatial organization and cell fate specification seen during normal development, including the formation of an anterior-posterior axis and germ layer–like structures, without the need for an intact embryo.

Typically, gastruloids are produced by aggregating embryonic stem cells or induced pluripotent stem cells in non-adherent culture conditions and exposing them to signaling cues that mimic developmental pathways. Activation of pathways such as WNT, NODAL/Activin, and FGF promotes symmetry breaking, elongation, and patterning. Over several days, these aggregates can polarize and express marker genes associated with mesoderm, endoderm, and ectoderm, with the T (Brachyury) gene commonly used as a readout for primitive streak–like activity. While mouse gastruloids often achieve clear axial elongation, human gastruloids can display more variable morphology but similarly reveal aspects of germ layer specification and axis formation.

Applications of gastruloids include studying the mechanisms of early patterning and germ layer formation, mapping gene regulatory networks, and evaluating the effects of genetic or pharmacological perturbations. They provide a controllable system to investigate developmental questions that are difficult to address in vivo and can be used in drug screening and toxicity testing. Limitations include incomplete recapitulation of the embryo, absence of extraembryonic tissues and maternal signals, variability between preparations, and ethical considerations for human-derived models. Gastruloids are tools for insight rather than direct substitutes for embryonic development.