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Processes in egg cell development investigated

During the growth and development of living organisms, different cell types must come into contact with each other in order to form tissues and organs together. A small team led by Prof. Dr. Anne Classen from the Cluster of Excellence CIBSS - Centre for Integrative Biological Signalling Studies at the University of Freiburg has discovered that complex shape changes during development are controlled exclusively by the affinity of cells to each other. The researchers investigated egg chambers of fruit flies (Drosophila melanogaster) and combined genetic methods with mathematical modelling. The study has been published in the journal Nature Communications.

07/12/2022

Complex organisational processes in the egg chamber

„We wanted to find out how different cell types organise themselves together to form functional units“, summarises Dr Vanessa Weichselberger, first author of the study and member of Classen's laboratory, the aim of her investigations. „The egg chamber is a good example of this, because different cell populations have to come together in it according to their function.“ The egg chamber is the structure in which an egg cell matures until it is ready for fertilisation. In Drosophila it looks like this: Inside is the growing egg cell on one side and 15 nurse cells on the other, which supply the egg cell with nutrients. In order to produce an egg, the egg cell must mature, while the nurse cells are eventually broken down.

Both processes, the maturation of the egg cell and the degradation of the nurse cells, are dependent on a thin layer of epithelial cells. The epithelial cells are therefore divided into specialised groups, which, due to their function, must be in contact with either the nurse cells or the egg cell. This partner-finding process between the inner and outer cells is a complex process that takes place while at the same time the conditions inside the cell are constantly changing.

What mechanisms can robustly control such a dynamic process was previously unknown,

says Classen.

Protein controls cell cohesion

The researchers had observed that the epithelial cells, which are specialised in the degradation of nurse cells, spread out and flatten out on the nurse cells. In doing so, they form a particularly large contact surface with the cells below. „This could be explained by an increased affinity between the two cell types,“ explains Weichselberger. „We therefore hypothesised that partner finding can be explained by simple mechanical attraction or repulsion processes.An increased affinity of a specialised part of the epithelial cells to the nurse cells would then lead to the remaining epithelial cells being displaced by the nurse cells and coming into contact with the egg cell. The researchers discovered that Eya, a protein that can control the activity of genes, influences the contact behaviour between the epithelial and nurse cells. If the researchers increased the concentration of Eya in epithelial cells, they increased their contact surface with nurse cells; if they switched off Eya, the contact surface was minimised.

Computer simulations

The developmental biologists used mathematical modelling to test their hypothesis. To do this, they worked together with Prof. Dr Patrick Dondl from the Faculty of Mathematics and Physics at the University of Freiburg. Dondl created computer models in which mechanical affinities of different strengths between the cells can be simulated. „Through mathematical modelling, we were able to show that an affinity change depending on Eya levels is sufficient to control the complex process of finding a partner," explains Weichselberger. „This meant that we could use Eya as a set screw to genetically control mate finding.“

By genetically modifying the Eya concentrations in epithelial cells and simulating these experiments in parallel on the computer, the researchers were able to test whether the Eya-regulated affinity between epithelial cells and nurse cells is responsible for mate choice. This showed that the manipulation of Eya alone can be used to specifically control which epithelial cells spread to the nurse cells and which epithelial cells come into contact with the egg cell. Thus, by regulating affinity, protein Eya is the main regulator of partnering between epithelial cells and nurse cells or oocytes. This also surprised Classen, who led the study: "The specific affinity is actually sufficient as a mechanism to control such complex developmental processes. And it is extremely flexible and robust, regardless of the volume of the egg chamber.

This mechanism is not exclusively limited to the egg chamber: the development of sperm cells in Drosophila mice is also dependent on Eya, which also controls the affinity between the inner sperm cells and the outer epithelial cells. Whether the results can also be transferred to other animals or humans is unclear.

To the Cluster of Excellence CIBSS

The Cluster of Excellence CIBSS – Centre for Integrative Biological Signalling Studies aims to gain a comprehensive understanding of biological signalling processes across scales: from the interactions of individual molecules and cells to the processes in organs and entire organisms.

Original publication: Weichselberger, V., Dondl, P., Classen, A.K. (2022). Eya-controlled affinity between cell lineages drives tissue self-organisation during Drosophila oogenesis. In:Nature Communications. DOI: https://doi.org/10.1038/s41467-022-33845-1

Source: LABO from 07.12.2022

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