Morphogenesis beyond in vivo

Morphogenetic events during development shape the body plan and establish structural foundations for tissue forms and functions. Acquiring spatiotemporal information of development, especially for humans, is limited by technical and ethical constraints. Thus, both stem cell-based, in vitro development models and theoretical models have been constructed to recapitulate morphogenetic events during development. These in vitro experimental and theoretical models offer accessibility, efficiency and modulability. However, their physiological relevance often remains obscure, owing to their simplistic nature, which obstructs their applicability as faithful and predictive models of natural development. We examine existing in vitro experimental and theoretical models of various developmental events and compare them with the current knowledge of natural development, with particular considerations of biomechanical driving forces and stereotypic morphogenetic features. We highlight state-of-the-art methods used to construct these in vitro models and emphasize the biomechanical and biophysical principles these models have helped unveil. We also discuss challenges faced by the current in vitro experimental and theoretical models and propose how theoretical modelling and in vitro experimental models should be combined with in vivo studies to advance fundamental understanding of development. Beyond in vivo models, stem cell-based in vitro models and theoretical models of morphogenesis have been constructed to recapitulate morphogenetic events during embryo development with heightened quantitative specificity. This Review discusses the accomplishments, challenges and opportunities of these models in promoting knowledge of mammalian development, including human development.