Speaker
Description
During brain morphogenesis, neurons extend axons over large distances along well-defined pathways. Axon pathfinding is regulated by both chemical and mechanical signals. However, we currently know very little about how these signals interact. We here show how local mechanical brain tissue properties contribute to guiding neuronal axons. In vivo time-lapse atomic force microscopy revealed stiffness gradients in developing brain tissue, which axons followed towards soft. Interfering with brain stiffness and mechanosensitive ion channels in vivo both led to aberrant neuronal growth patterns with reduced fasciculation and pathfinding errors. Tissue stiffness not only directly impacted neuronal growth but also indirectly by regulating neuronal responses to and the availability of chemical guidance cues in the surrounding tissue. The expression of long-range chemical guidance cues in both ex vivo multicellular tissues and in vivo brains was regulated by the stiffness of the environment, strongly suggesting that chemical and mechanical signaling pathways are intimately linked, and that their interaction is crucial for morphogenetic events.