Variability in when and how cells divide promotes healthy development in embryos

There is variability in when and how cells divide during the development of embryos. While researchers traditionally believed this variability was an obstacle that needed to be regulated, the Hiiragi group now found that it actually promotes healthy development. The results, published in Science on 11 October 2024, encourage other scientists to see the potential of variability and could have significant impact on assisted reproductive technology. 

An embryo consists of cells. These cells divide to make new cells, allowing the embryo to grow. The cells experience variability in how and when they divide and in how they interact with each other. Scientists traditionally believed that this variability was an obstacle to proper development of the embryo and needed to be filtered out. The Hiiragi group now published a study in Science suggesting otherwise. 

Development of embryos

“We found that the randomness in when and how cells divide actually helps embryos to develop properly,” says Dimitri Fabrèges, a postdoc researcher in the Hiiragi group. He and his colleagues studied embryos of mice, rabbits and monkeys and were surprised by what they found. “Even though the timing of cell divisions were random, the embryos still formed organized and functional structures,” Fabrèges explains. 

Interacting cells 

Every time cells divide and make new cells, an embryo grows. Consequently, all cells have to rearrange themselves in the growing embryo to form an organized structure. The Hiiragi group used so-called morphomaps to track how cells arrange themselves in space during development. Additionally, they analyzed how the cells physically interact with each other to form a connected structure – also called topology, and track how it changes in time and shapes the embryo. 

Healthy development

The researchers found that higher variability in cell division leads to a more optimal arrangement of cells within the embryo, which promotes healthy development. “Our work suggests that the variability in when and how cells divide and how they interact with each other is not just tolerated in the developing embryo. It actually plays a functional role in promoting robust development,” Fabrèges explains. 

Well-being of embryos

These results paint a radically different picture than was traditionally believed. “The role of variability in embryonic development is deeply overlooked in our field of research. But now, we show that it actually drives more precise and robust tissue development,” says Fabrèges. He and his colleagues hope that their study encourages other scientists to see the potential of variability. “It may even be possible that variability and topology are accurate predictors of the well-being of an embryo, which could have significant impact on assisted reproductive technology,” he concludes. 

About Takashi Hiiragi
Takashi Hiiragi is group leader at the Hubrecht Institute.  The Hiiragi group aims to understand what defines multi-cellular living systems. In particular, the group studies the design principle of tissue self-organization, using early mammalian embryos as a model system. To this end, they developed an experimental framework that integrates biology, physics and mathematics. Their recent studies led to a model in which feedback between cell fate, polarity, and cell and tissue mechanics underlies multi-cellular self-organization. The group adopts a wide variety of experimental strategies including embryology, genetics, advanced microscopy, biophysics, engineering and theoretical modelling, in order to address fundamental questions in cell and developmental biology. 

About the Hubrecht Institute

The Hubrecht Institute is a research institute focused on developmental and stem cell biology. Because of the dynamic character of the research, the institute as a variable number of research group, around 20, that do fundamental, multidisciplinary research on healthy and diseased cells, tissues and organisms. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), situated on Utrecht Science Park. Since 2008, the institute is affiliated with the UMC Utrecht, advancing the translation of research to the clinic. The Hubrecht Institute has a partnership with the European Molecular Biology Laboratory (EMBL). For more information, visit www.hubrecht.eu.