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Mechanosensing is critical for axon growth in the developing brain

Koser, David E; Thompson, Amelia J; Foster, Sarah K; Dwivedy, Asha; Pillai, Eva K; Sheridan, Graham K; Svoboda, Hanno; Viana, Matheus; Costa, Luciano da F; Guck, Jochen; Holt, Christine E; Franze, Kristian

Authors

David E Koser

Amelia J Thompson

Sarah K Foster

Asha Dwivedy

Eva K Pillai

Hanno Svoboda

Matheus Viana

Luciano da F Costa

Jochen Guck

Christine E Holt

Kristian Franze



Abstract

© 2016 Nature America, Inc., part of Springer Nature. All rights reserved. During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. However, growing neurons interact not only chemically but also mechanically with their environment. Here we identify mechanical signals as important regulators of axon pathfinding. In vitro, substrate stiffness determined growth patterns of Xenopus retinal ganglion cell axons. In vivo atomic force microscopy revealed a noticeable pattern of stiffness gradients in the embryonic brain. Retinal ganglion cell axons grew toward softer tissue, which was reproduced in vitro in the absence of chemical gradients. To test the importance of mechanical signals for axon growth in vivo, we altered brain stiffness, blocked mechanotransduction pharmacologically and knocked down the mechanosensitive ion channel piezo1. All treatments resulted in aberrant axonal growth and pathfinding errors, suggesting that local tissue stiffness, read out by mechanosensitive ion channels, is critically involved in instructing neuronal growth in vivo.

Citation

Koser, D. E., Thompson, A. J., Foster, S. K., Dwivedy, A., Pillai, E. K., Sheridan, G. K., …Franze, K. (2016). Mechanosensing is critical for axon growth in the developing brain. Nature Neuroscience, 19(12), 1592-1598. https://doi.org/10.1038/nn.4394

Journal Article Type Article
Acceptance Date Aug 25, 2016
Online Publication Date Sep 19, 2016
Publication Date Dec 1, 2016
Deposit Date Oct 22, 2019
Journal Nature Neuroscience
Print ISSN 1097-6256
Electronic ISSN 1546-1726
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 19
Issue 12
Pages 1592-1598
DOI https://doi.org/10.1038/nn.4394
Keywords General Neuroscience
Public URL https://nottingham-repository.worktribe.com/output/2919759
Publisher URL https://www.nature.com/articles/nn.4394
Additional Information Received: 29 June 2016; Accepted: 25 August 2016; First Online: 19 September 2016; Change Date: 3 October 2016; Change Type: Erratum; Change Details: In the version of this article initially published online, the equation in the last sentence of Methods section "In vitro time-lapse experiments," immediately following "When the third component of ...", contained a dot product. This should have been a cross product. The error has been corrected for the print, PDF and HTML versions of this article.; : The authors declare no competing financial interests.