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Nat Neurosci January 1, 2016; 19 (12): 1592-1598.
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Mechanosensing is critical for axon growth in the developing brain.

Koser DE , Thompson AJ , Foster SK , Dwivedy A , Pillai EK , Sheridan GK , Svoboda H , Viana M , Costa LD , Guck J , Holt CE , Franze K .

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.

PubMed ID: 27643431
PMC ID: PMC5531257
Article link: Nat Neurosci
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: fn1 piezo1

Article Images: [+] show captions
References [+] :
Atkinson-Leadbeater, Dynamic expression of axon guidance cues required for optic tract development is controlled by fibroblast growth factor signaling. 2010, Pubmed, Xenbase