Embryonic development begins once an egg cell is fertilized and starts to divide repeatedly. Initially appearing as a disorganized cluster, it eventually transforms into a well-structured entity. Recent research from an international team that includes scientists from the Institute of Science and Technology Austria (ISTA) sheds new light on this process, highlighting the essential roles of both chaos and order. These findings have been published in Science.
Embryonic development starts with the fertilization of a single egg cell, which then undergoes continuous division. Initially forming a disordered cluster, it matures into a tightly organized structure. A group of international researchers, including scientists from the Institute of Science and Technology Austria (ISTA), have offered new insights into this process, underlining the important contributions of chaos and order. Their findings are featured in Science.
Scientists engage in various activities, such as pipetting liquids into small test tubes, analyzing vast datasets, and reviewing research papers. However, stepping away from these routines is crucial for innovation. Taking a break from the lab environment can generate new ideas. For example, lab retreats foster interactions among peers that often lead to fresh collaborations.
This was the case for Bernat Corominas-Murtra and Edouard Hannezo from ISTA. Captivated by a dataset presented during a poster session at a research group retreat in Spain, Corominas-Murtra sparked an animated discussion with Dimitri Fabrèges, a postdoctoral researcher from Professor Takashi Hiiragi’s team at the Hubrecht Institute in Utrecht, Netherlands. What began as a discussion has now culminated in a publication in Science.
The international research team has created a comprehensive atlas of the early stages of mammalian morphogenesis — the development of shape and structure — by examining how embryos from mice, rabbits, and monkeys progress over time and space. Their analysis demonstrates that individual actions, such as cell divisions and movements, are quite chaotic, yet overall, embryos exhibit striking similarities. From this data, they propose a physical model explaining how mammalian embryos organize themselves from this chaos.
Transformation from singular to multiple
In the animal kingdom, embryonic development commences with the fertilization of an egg cell. This event instigates a series of cell divisions, commonly termed cleavages. To put it simply, one cell splits into two, two into four, four into eight, and this process continues. Eventually, the cells cluster into a well-organized formation called the blastocyst, which serves as a foundation for all future organs and tissues. This entire phenomenon is referred to as morphogenesis.
“The early stages of embryonic development are crucial as they lay the groundwork for all further developmental processes,” states Edouard Hannezo. For example, in C. elegans, a transparent roundworm and a prime model organism for developmental biology, the cell divisions in early embryos are highly regulated and consistently oriented across different specimens, resulting in organisms with identical cell counts. In contrast, mammalian species exhibit more randomness in division timing and orientation. This discrepancy raises inquiries about how mammalian embryonic development manages to be consistent despite this apparent disorder.
Creating a comprehensive embryo map
To investigate this question, the Hiiragi group aimed to image and quantitatively evaluate various embryos, assessing their similarities across different mammalian species, including mice, rabbits, and monkeys. Dimitri Fabrèges and his team developed a ‘morphomap’ — a visualization tool for complex morphological data. “It’s an imaging analysis framework illustrating how embryos behave spatially and temporally — a detailed atlas of embryo morphogenesis,” elaborates Hannezo.
This map empowered researchers to quantitatively study the developmental process and tackle questions regarding inter-embryo developmental variability. With this dataset, scientists could establish a benchmark for ‘normal’ morphogenesis.
Fabrèges showcased the morphomap during the lab retreat in Spain. The data revealed that the initial cell divisions following fertilization were not uniform in mice, rabbits, and monkeys, as cells divided in a seemingly random pattern until reaching the eight-cell stage, at which point all embryos began to resemble one another. “After appearing distinct at the early stages, embryos seemed to converge in shape by the end of the eight-cell stage,” explains Hannezo. But what is the cause of this convergence? What provides structure amidst the chaos?
A Rubik’s Cube of Embryos — Cluster Optimization
Theoretical physicists Corominas-Murtra and Hannezo were intrigued by this dataset and sought to understand the process from a theoretical perspective.
However, because the shape of an embryo is incredibly complex, discerning the similarity or disparity between two embryos posed a challenge. The researchers found that they could approximate the intricate structure of an embryo simply by examining how the cells interact with one another. “We believe that most critical details about an embryo’s shape can be inferred by understanding the arrangement of cells, or knowing which cells are directly connected – much like connections in a social network. This method greatly streamlines the data analysis and comparison of different embryos,” says Corominas-Murtra.
Utilizing this information, the researchers devised a straightforward physical model elucidating how embryos transition to a consistent shape. The model indicates that physical laws govern embryos to achieve a shared morphology found among mammals.
The model implies that by destabilizing most cell arrangements except a few targeted configurations, which reduces the embryo’s surface energy, physical interactions among cells guide the formation of a definitive shape. In essence, cells have a tendency to bond more closely over time, and this seemingly straightforward process causes the embryo to rearrange itself to attain optimal packing, akin to solving a Rubik’s Cube.
Interdependence of Chaos and Structure
The findings offer a comprehensive view of how mammalian embryo development is influenced by variability and resilience. Structure cannot exist without chaos, and both elements are crucial to the concept of ‘normal’ development. “We are beginning to acquire the tools necessary to investigate the variability of morphogenesis, which is vital for comprehending the mechanisms behind developmental robustness,” summarizes Hannezo. Randomness appears to be a key factor contributing to the complexity of life.
By enhancing our understanding of what is considered normal, scientists can also identify abnormalities. This knowledge could play a significant role in fields such as disease research, regenerative medicine, and fertility treatments. Looking ahead, this understanding may assist in identifying the healthiest embryos for in vitro fertilization (IVF), thus improving implantation success rates.
