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Axon zippering and its control by tension forces

Axon bundling plays an important role in the formation of brain circuits and peripheral nerves. This dynamical process is regulated by the competition of adhesive forces and mechanical tension in the axons.

During neural development, newly growing axons may bundle together or with previously grown axons, which helps them to achieve robust targeting. The bundles may form through a process in which the axons gradually adhere to each other in a way that resembles fastening a zipper. Such „axon zippering“ was only rarely described in the previous literature, and it was not clear how this process may be controlled. In collaboration with our French colleagues, we characterized this process and carried out a detailed biophysical analysis. We observed that in neural explants taken from the olfactory epithelium of mouse embryos, the growing axons formed a network of bundles that were gradually rearranged due to zippering processes. Using micromanipulations, pharmacological treatments, and mathematical modeling, we showed that the axon zippering and unzippering can be regulated by changes in mechanical tension – the internal force that stretches the axons. This study introduces a new role of mechanical tension in the development of the nervous system.



Fig. 1 Examples of axon zippers, imaged by scanning electron microscopy. (A) A simple zipper formed by two axon fascicles. Such a zipper may freely advance or recede, depending on the imbalance of the acting mechanical forces. (B) A zipper in which the axons are mutually entangled. Such a configuration does not readily unzipper.


Fig. 2 (A) A network of axons grown out of an explant of mouse embryonic olfactory epithelium (the explant is at left). (B) Following the application of fetal bovine serum, the cells in the explant contract and the axon network is stretched by pull to the left. This leads to a partial unzippering of axon bundles within the area marked in red.


Šmít, Daniel - Fouquet, C. - Pincet, F. - Zápotocký, Martin - Trembleau, A. Axon tension regulates fasciculation/defasciculation through the control of axon shaft zippering.  eLife. Roč. 6, Apr 19 (2017), č. článku e19907. ISSN 2050-084X, IF: 7.725, 2016