Epigenetics of the Locomotory System in Zebrafish

Movements are important. When animals move, they exert mechanical load on their bodies and their muscles and bones respond by the generation of more tissue. Vice versa, a lack of movement will result in a decrease in bone and muscle tissue.

During my PhD studies I have looked into the normal development of muscle and bone in the trunk of zebrafish. In addition, I have looked at different levels whether this development can be influenced by mechanical load. I investigated how cells respond to load by subjecting zebrafish cells to strain and observing the effects on cell morphology. The cells appear to orient themselves perpendicularly away from the strain, which results in a lower absolute strain value. During this orientation process, the expression of more than 400 genes is adjusted. In an entire organism I have investigated the normal development of bone and muscle. During development the muscle fibres turn away from the body axis and together they build up a spiral like architecture.

I have tried to explain this architecture by means of a computer model in which the equal work theory was implemented. According to this theory, the muscle fibres can only generate equal amounts of work when they can all shorten equally and by doing so function optimally.  The observed architecture appears to be adapted to the movement of the embryos in the egg and it is only generated after the embryos start moving.

From these observations I hypothesised that mechanical load, represented by the movements of the embryo, could be important for the normal development of the muscle architecture.

I tested this hypothesis by making use of mutant zebrafish embryos that are immobile. I found that the morphology of the embryos is indeed affected by this lack of movement, although the spiral like architecture does develop in the mutant embryos.

Finally, I made zebrafish larvae perform endurance training by making them swim against a water current. They developed more slow muscle in the trunk muscles, similar to endurance training in humans, but the heart muscle developed more fast muscle.

The general conclusion I can draw from the results in this thesis is that mechanical load already during early development is important for fine-tuning genetically predetermined principles.