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The mechanical control of neuronal development

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During the development of the nervous system, neurons migrate and grow over large distances. During these processes, they are exposed to a multitude of signals determining their growth velocities and direction. Currently, our understanding of neuronal development is, in large part, based on studies of biochemical signaling. Despite the fact that forces are involved in any kind of cell motion1-3, mechanical aspects have so far rarely been considered. We used compliant cell culture substrates, traction force microscopy and calcium imaging to investigate how Xenopus neurons respond to their mechanical environment. Axonal growth velocities, directionality, fasciculation, and maturation all significantly depended on substrate stiffness. Moreover, when grown on substrates incorporating linear stiffness gradients, axon bundles turned towards soft substrates. In vivo atomic force microscopy measurements revealed stiffness gradients in developing brain tissue, which axons followed as well towards soft. Interfering with brain stiffness and mechanosensitive ion channels in vivo both led to similar aberrant neuronal growth patterns with reduced fasciculation and pathfinding errors, strongly suggesting that neuronal growth is not only controlled by chemical signals – as it is currently assumed – but also by the tissue’s local mechanical properties.

Biography: Kristian Franze qualified as a veterinarian at the University of Leipzig in Germany, where he also obtained an advanced degree and PhD in physics in 2007. He then started his postdoc at the Cavendish Laboratory at the University of Cambridge. Since 2011, he is a lecturer at the Department of Physiology, Development and Neuroscience in Cambridge, holds an MRC Career Development Award, and is a Fellow at St. John’s College. His research focuses on how cellular forces and the mechanical interaction of cells with their environment control the development, functioning, and disorders of the nervous system.

References 1 Hardie, R.C., and Franze, K. (2012). Photomechanical responses in Drosophila photoreceptors. Science 338, 260-263. 2 Pagliara, S., Franze, K., Mcclain, C.R., Wylde, G.W., Fisher, C.L., Franklin, R.J., Kabla, A.J., Keyser, U.F., and Chalut, K.J. (2014). Auxetic nuclei in embryonic stem cells exiting pluripotency. Nat Mater 13, 638-644. 3 Betz, T., Koch, D., Lu, Y.B., Franze, K., and Kas, J.A. (2011). Growth cones as soft and weak force generators. Proc Natl Acad Sci U S A 108 , 13420-13425.

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