The institute's scientists developed a method that allows real-time monitoring of the development of embryos at the beginning of their journey and applied it for the first time to rabbits. The comparison they made between embryonic development in rabbits and mice gave rise to answers to fascinating questions about the formation of humans
While the differences between a human and a mouse or a chicken are obvious for all to see, at the beginning of their development there is a unique moment when a surprising similarity between them is revealed. Even skilled researchers have difficulty identifying whether embryos in a stage known as gastrulation will develop into a talking, chirping or croaking creature.
Embryos of different species begin their journey at different points of origin and of course develop into creatures with organs, features and sizes unique to each species - but at a certain moment they unexpectedly take on a very similar shape. Biologists describe this using the image of an hourglass (Hourglass model): like the sand that flows from container to container, the development of the embryos of all species in the vertebrate group - which includes mammals, fish, birds and reptiles - converges into a narrow bottleneck where it is almost identical.
Due to the difficulty of studying human embryos in the early stages of their development, scientists turn to model animals - mainly mice. The accepted assumption is that through the model animals it will be possible to learn about the exciting questions about embryonic development in humans. However, after about a century of in-depth acquaintance with mouse embryos, which yielded many important discoveries, we still know too little about the beginning of human life. Furthermore, it is not at all certain that the model of embryonic development in the mouse is sufficiently similar to its human counterpart, and it is not clear how much can be inferred from one to the other.
New research Offers a new approach to deciphering the mystery of embryo formation. The research of Dr Yonatan Stelzer and Dr. Yoav Misher from the Department of Molecular Biology of the Cell at the Weizmann Institute of Science, and of Ofir Raz and Prof. Loaded condition from the department of molecular biology of the cell and the department of computer science and applied mathematics at the institute - reveals new information about the beginning of the development of embryos and may help solve other open questions in the field. The researchers used a method they developed in a previous study, and which for the first time was able to describe the development of embryos over time. The method, which was applied in the previous study on mice, uses information collected from tens of thousands of individual cells, along with images and physical measurements of the embryos. This is how the researchers were able to assemble from discrete images a sort of continuous "film" that describes, hour by hour, how an embryo is formed.
In the current study, they returned to the method and faced a significant challenge that until now scientists had to ignore: the fact that embryonic development in mice deviates from that of other mammals, including humans. While the mouse embryo takes shape during the gastrulation stage in the form of an elongated cylinder, everything else looks like an almost flat disk. This fundamental geometric difference dictates different positions for the developing cells and tissues, at the fateful moments when the cells differentiate into nerve cells, become sex cells or begin to assemble the digestive system.
From the differences and similarities between mouse embryos and between the embryos of other mammals, fascinating questions arise that until now have been difficult to deal with: what is common and what separates the expressions of the genes and the development of cells and tissues in the cylindrical embryo of the mouse and the disc-shaped embryos? How do the genes and cells of such different creatures converge on similar behavior at a certain developmental moment? And is there any animal that can serve as a better model than a mouse to solve the mysteries of human development?
For this purpose, the researchers entered the rabbit hole. Although rabbits are very different from mice, even more so than it seems to the untrained eye, they share some common features with them, which make them a model animal from which a lot can be learned. First, the researchers repeated with the rabbits the process they carried out in the mice, and mapped the occurrences of the genes and the development of the cells and tissues, as they change over time. Next, they began identifying the exact characteristics of each cell and each developing tissue.
Prof. Tanai explains: "We used computer models to identify the genes and characterize the active cell types in the first stages of the development of the rabbit embryo. New technological tools allowed us to achieve in a short time extremely high levels of detail and accuracy - which previously took many years to reach in studies on the development of mice."
With the completion of the complex task, the researchers had at their disposal two "films" that document the creation of the cells and allow a meaningful comparison to be made: an examination of the real-time development of the embryos of two different creatures. The comparison revealed some instructive findings. First, a great similarity was discovered between the mouse and the rabbit in the expressions of the genes responsible for the development of the embryonic tissues in the convergence phase described by the hourglass model, and about 75 genes were identified that are central factors for this. The discovery attacks the hourglass model, and shows that despite the significant difference in the geometric shape of the embryos - their genes and cells behave in a remarkably similar manner. In this way, an initial hint is also given as to how the evolutionary processes that preserve the similar pattern in the gastrulation stage work - from which the huge variety of shapes that characterize the different species develops.
However, the researchers identified a great difference between the rabbit and the mouse in the development of the gametes - which both nature and researchers pay a lot of attention to because of their importance for the continuity of generations. A deeper acquaintance with the development of the rabbit's sex cells may also allow a better understanding of how they are formed in humans. Another big difference between the mice and rabbits was found in the extraembryonic tissues that are essential for the normal development of the embryos, the placenta and the yolk sac.
Dr. Shtelzer concludes: "The research presents computational and theoretical tools that are fertile ground for further research. The ability to compare in real time between different species has tremendous significance in the understanding of evolutionary processes. At the same time, the new information about the rabbit, which is probably more relevant to humans than the knowledge accumulated over the years about mice, will be able to shed light on the most elementary processes in the formation of humans and may contribute to applied and medical research."
Dr. Saifeng Cheng, Dr. Raz Ben Yair, Dr. Ron Hadas, Neta Raines, Dr. Marcus Mittenzweig, Oren Ben Kiki and Aviezer Lifshitz from the Institute participated in the study.
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