Long-range chemical signallingin vivois regulated by mechanical signals

Abstract

AbstractBiological processes are regulated by chemical and mechanical signals, yet the interaction between these signalling modalities remains unclear. Using the developingXenopus laevisbrain as a model system, we identified a critical crosstalk between tissue stiffness and chemical signallingin vivo. Targeted knockdown of the mechanosensitive ion channel Piezo1 in retinal ganglion cells (RGCs) led to pathfinding errorsin vivo.However, pathfinding errors were also observed in RGCs expressing Piezo1, when Piezo1 was downregulated in the surrounding brain tissue. Depleting Piezo1 in brain parenchyma led to decreases in the expression of the long-range chemical guidance cues, Semaphorin3A and Slit1, and markedly reduced tissue stiffness. While tissue softening was independent of Sema3A depletion, Slit1 and Sema3A expression increased significantly in stiffer environmentsin vitro. Moreover, stiffening soft brain regionsin vivoinduced ectopic Sema3A production via a Piezo1-dependent mechanism. Our results demonstrate that brain tissue mechanics modulates the expression of key chemical signals, a likely phenomenon across diverse biological systems.