C. elegans does not accidentally switch off its ability to detect salt

The worm is C. elegans. AMOLF is a credit.

AMOLF researchers and researchers from the MC have discovered a genetic mechanism that ensures that a nerve cell retains its identity once it has differentiated. A worm can detect salt. The identity of the cell is activated by a genetic switch. Jeroen van Zon and his colleagues have found a way to make this switch never switch off again. The research was published in a journal.

Every cell acquires its own identity during the development of an animal. The function of the genetic switches in the cell is activated during the development. The worm C. elegans has special nerve cells that detect salt in its environment, which is an example of a switch like this.

The switch is formed by the CHE-1Protein. The production of hundreds of different types of other proteins, which are responsible for detecting salt, is stimulated by thisprotein. The switch is switched on when CHE-1 is activated in the embryo. The worm can't detect salt without CHE-1. It is important that the switch is still on throughout the animal's life.

Van Zon and his student found out that the production of CHE-1 can vary in the cell. It should be possible for the switch to be switched off spontaneously due to chance fluctuations in the cell. They wondered why that didn't happen. Is it a real switch? They collaborated with Ser van der Burght, Suzanne rademakers and Gert Jansen to investigate the questions.

A strong connection.

The researchers showed that a genuine switch is involved.

The researchers used advanced genetic and microscopy techniques to study what would happen if they removed all CHE-1. If this system is a genuine switch, then they should be able to reactivate it by re-introducing the protein. If it's not a switch and the protein ensures a permanent change in the cell, then they should be able to remove it. The research showed that the switch is a genuine one. This is the first time that a genetic switch can be switched off. "What makes this work so striking is that we could use a simple manipulation to make a cell forget its identity, and by doing so, we revealed a major potential weakness in this type of switch."

The C. Elegans worm has a yellow box. The white dots are the same molecule. AMOLF is a credit.

Simulation discovers stability.

The switch stays in the on state under normal conditions. Computer simulations are used to investigate that. The concentration or binding strength of the CHE-1 protein is calculated by the computer.

If CHE-1 stimulates its own production far more strongly than all other proteins, the switch will remain activated for an extremely long period. If the amount of CHE-1 is very low, the production of those other proteins and the detection of salt are temporarily halted to make sure that the production rate of CHE-1 is restored. The switch remains on because of this self-enhancement effect.

A Mutant can't detect salt.

The outcomes correspond to the real-life situation after these discoveries. They did this by introducing a genetic change in the worm, which caused the production of CHE-1 to stop. In that case, the switch is quickly switched off and the animal can no longer detect salt.

Van Zon thinks that the mechanism of a stable switch could be used in other types of cells. People and animals have this type of switch. The question is whether this mechanism is widely spread. Is it possible to switch off our nerve cells by removing a single molecule? Do they use this mechanism to prevent this from happening during the many decades that these cells live for in our brains? We want to test this idea with other types of cells, first in C. elegans and later in other animals as well.

The mechanism of life-long maintenance of neuron identity despite molecular fluctuations is described by Joleen JH Traets and her colleagues. There is a DOI: 10.7554/eLife.

The journal has information on eLife.

C. elegans does not accidentally switch off its ability to detect salt.

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