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Poking Brains: the Mechanics of Neural Development

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Part of the TCSS Symposium

Neuronal growth is essential for nervous system development and is also required for regeneration after nervous tissue injury. As axons and dendrites grow towards their targets, they are guided by environmental cues, including a well-characterised set of biochemical signals. Recent in vitro studies suggest that neuronal growth can also be regulated by mechanical properties of the substrate. However, the role of mechanical cues in axon pathfinding in vivo, and the spatiotemporal dynamics of tissue mechanics during early nervous system development, are still largely unknown. Here we investigate the role of tissue stiffness in axon guidance within the early embryo, using the Xenopus laevis optic tract as a model system. Retinal ganglion cell (RGC) axons form the optic tract by growing from the embryonic retina, along a stereotypical path on the brain surface, and terminating at their target, the tectum. We have developed in vivo atomic force microscopy (AFM) to map tissue stiffness along the optic tract at different developmental stages. We find that the embryonic brain is overall mechanically inhomogeneous, and that brain stiffness changes over time. Specifically, we find that the elastic stiffness of the tectum is consistently lower than the rest of the path taken by RGCs. Our results indicate that the path of RGCs is correlated with stiffness gradients in vivo, before axon growth stalls after reaching the softer region. These findings are consistent with a role for substrate mechanics in axon pathfinding, which might not only be crucial during development but also during regenerative processes in the nervous system.

This talk is part of the Trinity College Science Society (TCSS) series.

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