Abstract
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.
Key points
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Pluripotent stem cell-based in vitro models and theoretical models can effectively recapitulate mammalian development, including those of topological and conformational morphogenesis.
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Pluripotent stem cell-based in vitro models can reconstitute essential aspects governing tissue morphogenesis, such as endogenous scales, exogenous stimuli and boundary conditions, and thereby provide mechanistic insights.
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Driven by state-of-art engineering tools, the geometry, stimuli and extracellular microenvironment of in vitro morphogenesis models can be modulated with heightened precision and specificity.
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Through combining in vitro and theoretical approaches, high-order complexity underlying morphogenetic dynamics can be decoupled and quantitatively studied.
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Acknowledgements
Studies in the Fu Research Group are supported by the Michigan-Cambridge Collaboration Initiative, University of Michigan Mcubed Fund, University of Michigan Mid-career Biosciences Faculty Achievement Recognition Award, National Science Foundation (PFI-TT 2213845, I-Corps 2112458, CMMI 1917304, CBET 1901718 and CMMI 2325361) and National Institutes of Health (R21 NS113518, R21 HD100931, R21 HD105126, R21 NS127983, R21 HD109635, R21 HD105192, R33 CA261696, R01 GM134535 and R01 NS129850). The authors apologize to colleagues whose work they could not cite owing to space restrictions.
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Y.L. and J.F. wrote the article text. Y.L. generated the figures. All authors contributed to the conceptualization of the article.
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Glossary
- Alveoli
-
Hollow, distensible cavities in lungs in which the exchange of oxygen and carbon dioxide occurs.
- Anencephaly
-
A congenital defect in the formation of neural tube, in which a baby is born without parts of the brain and skull.
- Blastocoel
-
A fluid-filled cavity inside pre-implantation embryos called blastocysts.
- Caudal
-
Towards the tail.
- Cleavage furrow
-
The indentation of the surface of a cell that begins the progression of membrane separation during cell division.
- Dorsal
-
Towards the back.
- Epiblast
-
Composed of pluripotent cells derived from inner cell mass in a blastocyst. It is located between hypoblast and trophoblast and gives rise to three definitive germ layers.
- Gastrulation
-
A morphogenetic process through which epiblast cells reorganize, differentiate and ultimately form three spatially organized germ layers, namely (dorsal to ventral) ectoderm, mesoderm and endoderm.
- Lateral
-
Away from the body midline.
- Lumen
-
A cavity or inner space enclosed by cells or tissues.
- Medial
-
Towards the body midline.
- Mesenchymal-to-epithelial transition
-
A biological process during which loosely connected mesenchymal cells reorganize, establish apical-basal polarity and transition into an assembly of closely packed epithelial cells. Its reverse process is called epithelial-to-mesenchymal transition.
- Neural plate
-
A region of ectoderm which contains a flat layer of columnar neuroepithelial cells.
- Neural tube
-
A tubular neural tissue and the precursor of the central nervous system.
- Neuromesodermal progenitor
-
A population of bipotent progenitor cells in the caudal region of the embryo. It contributes to both spinal cord and presomitic mesoderm development.
- Neurulation
-
Formation of neural tube, which involves two different morphogenetic processes. In primary neurulation, the neural plate folds inward until opposing edges come into contact, fuse and give rise to the neural tube. In secondary neurulation, cavities form in caudal neural precursors and later merge with the neural tube formed by primary neurulation.
- Respiratory diverticulum
-
A ventral outpouching structure that develops from the endodermal foregut and bifurcates into left and right lung buds. Lung buds are rudiments of two lungs and the left and right primary bronchi, and the diverticulum stem forms the trachea and larynx.
- Rostral
-
Towards the head.
- Somite
-
Segmented, block-like structures flanking the neural tube. They are the precursors to vertebrae, part of occipital bones of the skull, skeletal muscles, dermis, cartilage and tendons.
- Ventral
-
Towards the front.
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Liu, Y., Xue, X., Sun, S. et al. Morphogenesis beyond in vivo. Nat Rev Phys 6, 28–44 (2024). https://doi.org/10.1038/s42254-023-00669-x
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DOI: https://doi.org/10.1038/s42254-023-00669-x