In a study published in Nature Communications1, Marie Breau, a IBPS researcher
from Sylvie Schneider-Maunoury’s team2, found out that the axons of
the zebrafish olfactory sensory neurons, which establish connections with the
brain, elongate through an original mechanism involving mechanical forces exerted
on the neurons.
Using live imaging, the researchers discovered that the
olfactory axons extend through an unexpected mechanism : the cell bodies move
away from the axon tips which remain stationary, anchored to the brain surface.
This wiring strategy differs from the classical mode of axon elongation, in
which the axon tip (the growth cone), emerges from a static cell body and navigates
in the embryo in response to guidance molecules. Here, the axon extends through
the displacement of the cell body.
To better understand how this movement is regulated, the
researchers analyzed the role of cytoskeleton components, including microtubules
and actomyosin. They show that, surprisingly, the displacement of the cell
bodies is independent from the intracellular cytoskeleton : it is a passive
process, likely triggered by extrinsic mechanical forces that push or pull the cell
bodies, forcing them to move away from their tethered axon tips.
To characterize in more detail the mechanical forces
involved, the researchers used laser ablation to establish a tension map in the
developing neuronal circuit. The map further supports the idea that the cell
bodies of the olfactory neurons undergo compression or traction forces driving their
Caption : In the left, a schematic view of canonical axon growth : the axon extends through the locomotor activity of its growth cone, in response to molecular signals present in the environment. On the right, the new mode of axon elongation discovered by the researchers : the axon extends through the passive displacement of the cell body away from the anchored axon tip, in response to extrinsic pushing or pulling mechanical forces.
This study thus highlights an original mechanism of neuronal
circuit formation, in which axon extension is driven by mechanical forces exerted
on the neurons. This finding has strong implications in the developmental
neurobiology field : it reveals the importance of mechanical signals in the
development of the nervous system, which was thought to be mostly controlled by
molecular cues guiding neuronal migration and axon growth.
Other instances of axon elongation with static axon
tip have been reported. For example, during the late phases of development, after
the synaptic contacts have been established, the axons keep elongating to follow
the continuous growth of the organism. It has been proposed that this crucial
and universal phase of axons extension is controlled by mechanical tension
imposed tissue growth, but this hypothesis has not been tested yet. The zebrafish
olfactory circuit represents an amenable system in which to explore the
dynamics and mechanisms underlying this general mode of axon elongation in
response to extrinsic mechanical forces. On a longer term, these findings might
help to design new tissue engineering methods dedicated to brain and spinal
This study has been published online on the INSB
1. Extrinsic mechanical forces mediate retrograde axon extension in a developing neuronal circuit, Breau MA, Bonnet I, Stoufflet J, Xie J, De Castro S, Schneider-Maunoury S. Nature Communications.
2. Equipe Morphognèse du cerveau des vertébrés (UMR 7622, Inserm U1156)