During nervous system development, molecular signals are apparently not the only signals to allow neurons to extend their axons and create connections with other nerve cells. Mechanical forces, which are still poorly understood, can also play a determining role.
It is classically accepted that the axon of a neuron is formed by emerging from a static cell body, and then it navigates towards its target in response to guiding molecules. A team* from the Paris-Seine Institute of Biology, hoping to view this process in vivo, discovered the existence of another mechanism: external mechanical forces applied to the neuron, leading to the passive movement of the cell body, which extends its axon in as a result.
The Morphogenesis of the Brain of Vertebrates team, led by Sylvie Schneider-Maunoury, discovered this original mechanism after it began examining the olfactory sensory neurons in zebrafish. These neurons must establish connections with the brain as they develop. Marie Bréau, who led the research, explains: “The zebrafish is ideal for filming the development dynamic in real time, since the embryos are transparent and develop outside the mother’s body. On top of this, it is easy to make them express fluorescent proteins that can be observed with a confocal microscope.”
After filming the nerve tissue over a total of ten hours, the researchers observed that the olfactory axons grow longer in response to the movement of the cell bodies. The cell bodies move away from the tips of their axons, while the axons remain in place since they are anchored to the surface of the brain. This phenomenon is different from traditional axon elongation!
A Passive Process that Involves External Forces
To better understand how cell bodies produce movement, the researchers analyzed the role of the components of the neuron cytoskeletons, which are known for controlling the migration of these cells in other contexts. They noticed that the movement of these cell bodies does not depend on the intracellular cytoskeleton: it is a passive process that requires no internal motor. This suggests that mechanical forces outside the neurons are pushing or pulling the cell bodies, moving them further away from the tips of their axons.
The researchers characterized the mechanical forces in the presence of other factors: “The mechanical tension map that we obtained reinforces the idea that forces of traction or compression are being exerted on the cell bodies and are the cause of their movements,” explains the scientist. The provenance of these forces—Neighboring neurons? Adjacent tissues?—remains to be determined. This is the aim of the research to come. “We would also like to understand how these mechanical forces play out as molecular responses inside the neurons, particularly how the axon recruits the material required for its elongation under their impact.”
The system studied here could also help us understand how axons lengthen as the organism grows, once the nerve connections have been established. Is this another instance of axons lengthening in response to mechanical forces? Far from being solely basic, this discovery could also contribute to technical advances in tissue repair: “Today, the success of engineering methods that aim to repair the nervous system remains limited. Eventually, our research could help develop new approaches to tissue engineering devoted to repairing the brain and spinal cord, using neuron responses to mechanical forces,” concludes Marie Bréau.
*Inserm unit 1156/CNRS/UPMC, Paris-Seine Institute of Biology, vertebrate brain morphogenesis team
MA Breau et al. Extrinsic mechanical forces mediate retrograde axon extension in a developing neuronal circuit. Nature Communications, August 17, 2017