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

TLDR

During embryogenesis, organisms acquire shape under boundary conditions that impose geometrical, mechanical, and biochemical constraints, yet a detailed integrative understanding of how these modules pattern and shape the mammalian embryo remains lacking due to inaccessibility for direct observation. These impediments are circumvented by engineering embryo‑like structures (stembryos) from pluripotent stem cells that are easy to access, track, manipulate, and scale, allowing identification of minimal sets of mechanical and biochemical inputs required to pattern and shape the mammalian embryo. We show that controlled modulation of the cellular environment, together with precise measurements and manipulations of tissue biochemistry, mechanics, and geometry across spatial and temporal scales, reveals mechanochemical feedback loops governing embryo morphogenesis. Even without active manipulations, stembryos display intrinsic phenotypic variability that can be leveraged to define constraints ensuring reproducible morphogenesis in vivo.

Abstract

ABSTRACT 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.