How do cells find the right mate?

During the growth and development of living organisms, different types of cells must come into contact with each other in order to form tissues and organs
together.
A small team in collaboration with Prof.
Prof.
Anne Classen of the CIBSS-Integrated Biosignal Research Centre at the University of Freiburg found that complex changes in form or morphology during development are driven solely by
the affinity of cells for each other.
The researchers examined the egg chambers of the fruit fly (Drosophila melanogaster) and combined genetic methods and mathematical modeling
in their work.
The study was published in
the scientific journal Nature Communications.

The process of ovan chamber tissue is complex

Dr.
Vanessa Weichselberger, lead author of the study and a member of the Klassen lab, summarizes the team's work: "We wanted to find out how different types of cells organize each other's morphogenesis to form functional units
.
The egg chamber is a good example because inside it, different cell populations must self-organize into functions
.
"The egg chamber is a structure
in which an immature egg cell or oocyte matures until it is ready for fertilization.
The egg chamber of the fruit fly looks like a small football
ball.
Inside, the growing egg cells are located on one side, and on the other side are the 15 care cells that provide nutrition to the immature egg cells
.
In order to produce eggs, the egg cells must mature and the care cells are eventually removed
.

Both processes of egg cell maturation and care cell removal rely on the outer epithelial cell layer
.
For this, epithelial cells are divided into specific groups which, depending on their function, must come into contact
with care cells or egg cells.
The pairing of internal and external cells is a complex process, and the relationship between the size of the egg cavity is constantly changing
.
"Until now, we didn't know the mechanism
that could strongly control this dynamic process," Classen said.

Eya controls cellular affinity

The researchers observed that epithelial cells that specifically remove care cells unfolded and flattened
on the care cells.
This creates a particularly large contact area
with the care cells below.
Weichselberger explains: "This can be explained
by the enhanced affinity between the two cell types.
So we hypothesize that the matching of internal and external cells occurs
through a simple mechanical process of attraction and repulsion.
"The high affinity of a special group of epithelial cells for the care cells causes the rest of the epithelial cells to transfer from the care cells to the
egg cells.
The researchers found that a protein called Eya controls the activity of genes that affect the behavior of contact between
epithelial cells and care cells.
If the researchers increased the concentration of Eya in epithelial cells, the area of contact surfaces between these cells and the care cells increased
.
If they removed Iya, the contact surface was minimized
.

Cell affinity plays a decisive role in development

To test their hypothesis, developmental biologists used mathematical models
.
To do this, they collaborated
with Prof.
Dr.
Patrick Dondl from the Faculty of Mathematics and Physics of the University of Freiburg.
Dondl built mathematical models that could simulate different degrees of mechanical affinity
between cells.
Weichselberger explains: "The mathematical model allowed us to demonstrate that changes in affinity dependent on Eya levels are sufficient to control complex processes
that match cell types.
This means that we can use Eya as a fixing screw to genetically control the position of the
partner.
”

Very flexible and robust

By genetically altering the concentration of Eya in epithelial cells and simulating these experiments in a vita, the researchers were able to test whether the Eya-regulatory affinity between epithelial cells and care cells was responsible for self-organization
.
They observed that just by manipulating Eya, they could deliberately control which epithelial cells spread on the care cells and which came into contact
with the egg cells.
This suggests that Eya is a major regulator of self-organization between epithelial cells and internal cells (i.
e.
, care cells and egg cells
) through affinity.

Classen explains: "As a mechanism that controls this complex developmental process, specific affinity is actually sufficient
.
In a way, it is very flexible, robust and independent of the volume
of the egg chamber.
”

Men have a similar process

This mechanism is not limited to the egg chamber
.
The development of male Drosophila sperm cells also depends on Eya
.
Here, too, the protein Eya controls the affinity between the developing internal sperm cells and the outer epithelial cells
.
It's unclear whether these results also apply to other animals or humans
.
But during oovogenesis in other species, similar structures and developmental processes make this seem possible
.

 Eya-controlled affinity between cell lineages drives tissue self-organization during Drosophila oogenesis.