title: Mechanosensing is critical for axon growth in the developing brain.
abstract: 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.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Koser
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Amelia J
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Foster
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Asha
authors.initials: A
authors.lastname: Dwivedy
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Eva K
authors.initials: EK
authors.lastname: Pillai
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Graham K
authors.initials: GK
authors.lastname: Sheridan
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Hanno
authors.initials: H
authors.lastname: Svoboda
authors.affiliation: São Carlos Institute of Physics, University of São Paulo, São Carlos, Brazil.
authors.forename: Matheus
authors.initials: M
authors.lastname: Viana
authors.affiliation: São Carlos Institute of Physics, University of São Paulo, São Carlos, Brazil.
authors.forename: Luciano da F
authors.initials: LD
authors.lastname: Costa
authors.affiliation: Department of Physics, Cavendish Laboratory, University of Cambridge, Cambridge, UK.
authors.forename: Jochen
authors.initials: J
authors.lastname: Guck
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Holt
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.|Department of Physics, Cavendish Laboratory, University of Cambridge, Cambridge, UK.
authors.forename: Kristian
authors.initials: K
authors.lastname: Franze
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000254:growth & development*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells; D014795:Visual Pathways / Q000254:growth & development*; D014982:Xenopus laevis; D015027:Zebrafish