Methods for modelling development: Nature Methods method of the year 2023

How a new organism can develop and what goes wrong in the context of congenital disorders has fascinated men for centuries. Both developmental biologists and clinicians alike aim at unravelling the secrets of reproduction with the ultimate goal to understand the process of development at molecular level and develop strategies to support reproductive medicine in the long-term.

Development is a highly complex process that requires the precise interplay between various entities to ultimately form a proper embryo consisting of various cell and tissue types. One main challenge in the study of embryonic development is the access to suitable model systems. Each model system has its own advantages and limitations. Cells in a dish for instance can be a clean system to study how cells can be instructed to differentiate, but they don’t recapitulate the whole embryo and its surroundings. And while embryos from model animals do enable the study of the whole embryo, there are obviously differences between these animals and humans. Lastly, research on human embryos is limited due to the ethical considerations related to their use, and their limited availability.

Embryo-like structures

Over the last years, in vitro models of embryonic development, or embryo-like structures, have been established that each recapitulate certain stages of embryonic development. These model systems are generated from stem cells: unspecified cells that can be maintained in the lab for a long time. These in vitro models have several advantages: they can be generated in large numbers, can be genetically manipulated to study the function of specific genes and they even allow the study of human development. This revolutionizes the field of developmental biology and now allows the in-depth analysis of development down to the molecular level. For this reason, Nature Journal has selected “methods for modelling development” as “Method of the Year 2023”. These methods clearly have a major impact on the scientific community, and also on society in terms of the potential to develop medical interventions in the future. Politicians, clinicians, ethicists and developmental biologists are re-evaluating and updating the Dutch embryo law to ensure that these embryo-like structures will continue to be used in an ethically responsible way in the future.

In vitro and in silico models

For Nature Methods, scientific writer Vivien Marx has discussed with Ina Sonnen from the Hubrecht Institute and other experts in the field of developmental biology on how such embyo-like models shape the future of developmental biology¹. Marx also interviewed Nicolas Rivron, who developed blastoids during his time at the Hubrecht Institute. Blastoids are an embryo-like structure that aims to recapitulate the pre-implantation stage of development².

In her article, Marx highlights the potential to build in silico models of embryonic development. These are computer models that are based on findings from the lab. On the one hand, they can support and validate experimental findings. On the other hand, they can be used to test hypotheses at the computer before turning to experiments with animal models. Such computer-based models can be used in conjunction with in vitro models in the dish to dissect embryonic development in ever deeper experimental detail.

Despite the fact that the establishment of such in vitro and in silico models of embryonic development is a major step in developmental biology, they only recapitulate certain aspects of development – not the full complexity of a developing organism. The article therefore ends with the conclusion that it will always be essential to compare findings from in vitro models to the “real” in vivo system.

Models of development at the Hubrecht Institute

Here at the Hubrecht Institute, we study embryonic development from molecular up to the organismal level. We have contributed to the development of in vitro models of pre-implantation development, so called blastoids², as well as models for post-implantation development, so called gastruloids^3,4. Finally, we are pioneering in the establishment of in vitro models of organ formation, called organoids. These are mini-organs that recapitulate certain aspects of the organ^5,6 and can be used to study healthy functioning of the organ and disease.

Hubrecht research groups working with gastruloids, blastoids and organoids

Sonnen group (gastruloids and blastoids)
Van Oudenaarden group (gastruloids)
Kind group (gastruloids and blastoids)
Rivron group (former Hubrecht research group that set up the blastoid system)
Organoid group (previously called Clevers group – set up the organoid system)

Sources

1 Marx, V. How to build a virtual embryo. Nat Methods 20, 1838-1843, (2023).
2 Rivron, N. C., Frias-Aldeguer, J., Vrij, E. J., Boisset, J.-C., Korving, J., Vivié, J., Truckenmüller, R. K., van Oudenaarden, A., van Blitterswijk, C. A. & Geijsen, N. Blastocyst-like structures generated solely from stem cells. Nature 557, 106-111, (2018).
3 van den Brink, S. C., Alemany, A., van Batenburg, V., Moris, N., Blotenburg, M., Vivie, J., Baillie-Johnson, P., Nichols, J., Sonnen, K. F., Martinez Arias, A. & van Oudenaarden, A. Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids. Nature 582, 405-409, (2020). Or read a summary on our website.
4 Moris, N., Anlas, K., van den Brink, S. C., Alemany, A., Schroder, J., Ghimire, S., Balayo, T., van Oudenaarden, A. & Martinez Arias, A. An in vitro model of early anteroposterior organization during human development. Nature 582, 410-415, (2020). Or read a summary on our website.
5 Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J. & Clevers, H. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262-265, (2009).
6 Gupta, A., Lutolf, M. P., Hughes, A. J. & Sonnen, K. F. Bioengineering in vitro models of embryonic development. Stem Cell Reports 16, 1104-1116, (2021).