Axon tension regulates fasciculation/defasciculation through the control of axon shaft zippering

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Abstract

While axon fasciculation plays a key role in the development of neural networks, very little is known about its dynamics and the underlying biophysical mechanisms. In a model system composed of neurons grown ex vivo from explants of embryonic mouse olfactory epithelia, we observed that axons dynamically interact with each other through their shafts, leading to zippering and unzippering behaviour that regulates their fasciculation. Taking advantage of this new preparation suitable for studying such interactions, we carried out a detailed biophysical analysis of zippering, occurring either spontaneously or induced by micromanipulations and pharmacological treatments. We show that zippering arises from the competition of axon-axon adhesion and mechanical tension in the axons, and provide the first quantification of the force of axon-axon adhesion. Furthermore, we introduce a biophysical model of the zippering dynamics, and we quantitatively relate the individual zipper properties to global characteristics of the developing axon network. Our study uncovers a new role of mechanical tension in neural development: the regulation of axon fasciculation.

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Daniel Šmít

Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

Competing interests
The authors declare that no competing interests exist.
Coralie Fouquet

Neuroscience Paris Seine - Institute of Biology Paris Seine, Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, Paris, France

Competing interests
The authors declare that no competing interests exist.
Frédéric Pincet

Laboratoire de Physique Statistique, Ecole Normale Superieure, PSL Research University, Paris, France

Competing interests
The authors declare that no competing interests exist.
Martin Zapotocky

Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

For correspondence
zapotocky@biomed.cas.cz

Competing interests
The authors declare that no competing interests exist.
Alain Trembleau

Neuroscience Paris Seine - Institute of Biology Paris Seine, Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, Paris, France

For correspondence
alain.trembleau@upmc.fr

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8290-0795

Funding

Université Pierre et Marie Curie

Frédéric Pincet
Alain Trembleau

Czech Science Foundation (14-16755S)

Martin Zapotocky

Institut National de la Santé et de la Recherche Médicale

Alain Trembleau

Centre National de la Recherche Scientifique

Frédéric Pincet
Alain Trembleau

Agence Nationale de la Recherche (ANR-2010-BLAN-1401-01)

Alain Trembleau

National Institutes of Health (5R01DC012441)

Alain Trembleau

First Faculty of Medicine at Charles University (GAUK 396213)

Martin Zapotocky

Agence Nationale de la Recherche (ANR-11-IDEX-0004-02)

Alain Trembleau

Barrande Czech-French Cooperation program (7AMB12FR002)

Alain Trembleau

Czech Academy of Sciences (RVO#67985823)

Martin Zapotocky

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Procedures involving animals and their care were conducted according to European Parliament Directive 2010/63/EU and the 22 September 2010 Council on the protection of animals.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.