Sculpting with stem cells: how models of embryo development take shape

During embryogenesis, organisms acquire their shape given boundary conditions that impose geometrical, mechanical and biochemical constraints. A detailed integrative understanding how these morphogenetic information modules pattern and shape the mammalian embryo is still lacking, mostly owing to the inaccessibility of the embryo in vivo for direct observation and manipulation. These impediments are circumvented by the developmental engineering of embryo-like structures (stembryos) from pluripotent stem cells that are easy to access, track, manipulate and scale. Here, we explain how unlocking distinct levels of embryo-like architecture through controlled modulations of the cellular environment enables the identification of minimal sets of mechanical and biochemical inputs necessary to pattern and shape the mammalian embryo. We detail how this can be complemented with precise measurements and manipulations of tissue biochemistry, mechanics and geometry across spatial and temporal scales to provide insights into the mechanochemical feedback loops governing embryo morphogenesis. Finally, we discuss how, even in the absence of active manipulations, stembryos display intrinsic phenotypic variability that can be leveraged to define the constraints that ensure reproducible morphogenesis in vivo.

Automated summary

During embryogenesis, organisms develop their shape under various constraints imposed by geometry, mechanics, and biochemistry. Understanding the mechanisms that pattern and shape the mammalian embryo is challenging due to the inaccessibility of live embryos for direct observation. Developmental engineering of embryo-like structures from pluripotent stem cells provides a way to study these mechanisms. By modulating the cellular environment, researchers can identify the essential mechanical and biochemical inputs required for embryo patterning and shaping. Further studies on tissue biochemistry, mechanics, and geometry at different scales can provide insights into the mechanochemical feedback loops governing embryo morphogenesis. Additionally, inherent phenotypic variability in stembryos can be leveraged to understand the constraints that ensure reproducible morphogenesis in vivo.