Virtual embryo with cellular resolution

Drosophila embryos were disassembled into several thousand individual cells, and then put back together – but already in a computer

Anastasia Subbotina, "Science and Life"

At an early stage of development, any embryo is a microscopic handful of cells. They all look the same under a microscope, but each already knows which tissue it will give rise to, who its descendants will be – neurons, muscle cells or someone else. How do embryonic cells know their fate, where does the complexity and diversity of a multicellular organism come from if it "starts" with a single cell - these questions have occupied the minds of more than one generation of researchers. 

One of those who tried to answer them was Alan Turing, an outstanding mathematician and logician who stood at the origins of computer science. At his time, almost nothing was known about the molecular principles of genes, however, Turing understood that there are certain chemicals in cells that can be distributed unevenly through the tissue, so that their concentration will increase in some directions, and decrease in others (in other words, concentrations will be distributed by gradients). 

He suggested that such differences in concentration could somehow turn into differences in cellular "self-determination". Later it became clear that chemicals are products of gene expression, that is, proteins, and that their distribution throughout the cell (that is, spatial chemical gradients) is really exactly what allows cells to understand where they are in the embryo and choose their own path of development. 

Over time, much in the development of a living organism has become clear, and in general, embryogenesis no longer seems an inexplicable miracle (at least for those who take the trouble to learn something on the topic). But alas, at the same time it became clear that this process does not have a concise and legible explanation. Each event in it is caused by so many factors, such complex mutual influences of various genes and environmental conditions that in order to present a complete picture of the development of the embryo, it is necessary to connect information technologies. 

This is exactly what they did at the Berlin Institute of Medical Systems Biology, part of the Max Delbruck Center for Molecular Medicine. The researchers worked with a fruit fly embryo, which after the first thirteen synchronous cell divisions consists of 6000 cells. A virtual three-dimensional model with cellular resolution was created for the embryo. In each of its cells, data on the activity of about 8000 genes were stored, so that the model allowed to recreate their three-dimensional gradients in the virtual body of the embryo, observing how much they overlap with each other. The full results of the research are published in Science. 

A real fruit fly embryo, in which body parts begin to form: on the left you can see how the head begins to separate from the trunk. (Photo: Philipp Wahle, BIMSB at the MDC.)

A virtual fruit fly embryo in several projections; the activity of different genes is shown in different colors. (Illustration: Drosophila Virtual Expression eXplorer, BIMSB at the MDC.)

To get their virtual "pet", the researchers first had to disassemble into individual cells about five thousand embryos that are at the same stage of development. Then they read all the matrix RNA (mRNA) molecules in each cell – as we know, genetic information from DNA is copied into matrix RNA, which is then used by protein synthesis machines; in other words, knowing how many and which mRNAs float in the cell, we can judge with a high degree of confidence which the genes in the cell are active, and which ones are not. The RNA data was transformed into virtual cells, from which a 3D embryo was then reconstructed; naturally, it was not without a special software algorithm that had to be created specifically for this task. 

According to Nikolaus Rajewsky, the head of one of the scientific groups that worked on the embryo model, molecular genetic processes can now be studied not only in painstaking and long-term experiments with real embryos, but also in virtual experiments. The work, which can take years when using traditional research methods, can now be completed in a couple of hours. 

Despite the fact that humans and fruit flies are quite different from each other, most of the fundamental biological mechanisms that control embryonic development have remained unchanged throughout the many millions of years of evolution that separate us. And most of what we know in the field of developmental biology has been obtained in experiments on model animals, such as mice and fruit flies. 

Our ideas about human embryonic development – especially this applies to the late stages, which for ethical reasons cannot be studied on human embryos – are very often nothing more than an extrapolation of the results obtained on animals. Therefore, the three–dimensional model of the embryo created by the researchers is relevant not only to flies - since modern embryology owes its success to experiments on fruit flies, the virtual fruit fly will seem to be a pretty "cool" tool. 

By the way, we need embryology and developmental biology not only for the sake of the embryos themselves, from which we will obviously learn to correct various developmental defects in the near future. Let's not forget that all regenerative medicine is based on stem cells, and the knowledge about stem cells, about their relationship with each other and with other types of cells belong to the biology of development. 

If we want to stimulate tissue regeneration at the site of injury or even grow an organ "from scratch", it is necessary to understand which genes work here and how they interact with each other. But the processes that are activated during tissue regeneration are very similar to what happens when this tissue occurs during embryogenesis. Therefore, for example, wound healing is quite successfully studied on the same fly embryos. 

Returning to the 3D embryo, it is worth noting that so far such a model has been built for only one time point. To get a more detailed model of embryonic development, the authors of the work are going to do the same, but for an embryo at other stages of development, which has already begun to form organs. 

Portal "Eternal youth" http://vechnayamolodost.ru  06.09.2017