Development in a Dish—In Vitro Models of Mammalian Embryonic Development

Abstract

Despite decades of research, the complex processes of embryonic development are not fully understood. The study of mammalian development poses particular challenges such as low numbers of embryos, difficulties in culturing embryos in vitro, and the time to generate mutant lines. With new approaches we can now address questions that had to remain unanswered in the past. One big contribution to studying the molecular mechanisms of development are two- and three-dimensional in vitro model systems derived from pluripotent stem cells. These models, such as blastoids, gastruloids, and organoids, enable high-throughput screens and straightforward gene editing for functional testing without the need to generate mutant model organisms. Furthermore, their use reduces the number of animals needed for research and allows the study of human development. Here, we outline and discuss recent advances in such in vitro model systems to investigate pre-implantation and post-implantation development.

Signalling dynamics in embryonic development

“…With new technological developments, the mechanistic investigation of the role of signalling dynamics becomes amenable. (1) In vitro models of embryonic development and adult tissue homeostasis, including stem cell-based embryo-like structures and organoid models, that can be generated in high numbers, enable the study of signalling dynamics in accessible and simplified systems [228,229]. (2) Signalling reporters allow the spatiotemporally resolved quantification of signalling dynamics.…”

Developmental toxicity of remdesivir, an anti‐COVID‐19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells

“…To assess the developmental toxicity of chemicals, in vitro assays using pluripotent stem cells have been explored. Because pluripotent stem cells are capable of self‐renewal and differentiation into various types of tissues, they have been used as investigative tools to model embryo development in vitro (El Azhar & Sonnen, 2021 ). The basic principle of stem cell‐based assays is that the adverse effects of chemical exposures on in vitro differentiation are interpreted as a sign of developmental toxicity (Riebeling et al, 2012 ).…”

Archetypal Architecture Construction, Patterning, and Scaling Invariance in a 3D Embryoid Body Differentiation Model

“…Previous studies facilitated the development of efficient protocols for in vitro pluripotent stem cell differentiation to reconstruct the developmental trajectories for multiple cell types ( Oh and Jang, 2019 ; El Azhar and Sonnen, 2021 ; van den Brink and van Oudenaarden, 2021 ). Numerous 2D and 3D engineered embryonic cell models allowed the investigation of the developmental mechanisms at different levels previously studied only in animal embryos ( Camacho-Aguilar and Warmflash, 2020 ).…”

“…Numerous 2D and 3D engineered embryonic cell models allowed the investigation of the developmental mechanisms at different levels previously studied only in animal embryos ( Camacho-Aguilar and Warmflash, 2020 ). However, regardless of the significant progress in creating and studying embryo-like models, there are remain insufficiently explored possible 3D morphological archetypes generated by combining different embryonic cells and the cellular mechanisms coordinating the architecture construction ( Renner et al, 2017 ; Sozen et al, 2018 ; Zheng et al, 2019 ; van den Brink et al, 2020 ; Zhu and Zernicka-Goetz, 2020 ; El Azhar and Sonnen, 2021 ; Guo et al, 2021 ; Jerber et al, 2021 ; Molè et al, 2021 ). Therefore, further studies of the 3D embryonic cell models with different “starting” cell populations, including cancer cells, are needed for disclosing the mechanisms of morphogenesis and architecture construction in different environments.…”