Activity-dependent development of the body's touch receptors.

Abstract

We report a role for activity in the development of the primary sensory neurons that detect touch. Genetic deletion of Piezo2, the principal mechanosensitive ion channel in somatosensory neurons, caused profound changes in the formation of mechanosensory end-organ structures. Peripheral-nervous-system-specific deletion of the voltage-gated sodium channel Na_v1.6 (Scn8a), which resulted in altered electrophysiological responses to mechanical stimuli, also disrupted somatosensory neuron morphologies, supporting a role for neuronal activity in end-organ formation. Single-cell RNA sequencing of Piezo2 mutants revealed changes in gene expression in sensory neurons activated by light mechanical forces, whereas other neuronal classes were minimally affected, and genetic deletion of Piezo2-dependent genes partially reproduced the defects in mechanosensory neuron structures observed in Piezo2 mutants. These findings indicate that mechanically evoked neuronal activity acts early in life to shape the maturation of mechanosensory end-organs that underlie our sense of gentle touch.