Activity-dependent development of the body's touch receptors
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 Nav1.6 (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 the 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. Overall design: Dorsal root ganglia from segmental levels C2 and below were dissected and dissociated to obtain neurons for single cell RNA sequencing analysis. In the first bioreplicate, DRG from two Cdx2-Cre/+; Piezo2flox/flox animals (age P24) were dissected and assigned as “Mutant sample 1” and DRG from three control littermates were dissected on the same day and assigned as “Control sample 1.” In the second bioreplicate, DRG from three Cdx2-Cre/+; Piezo2flox/flox animals (age P21) were dissected and assigned as “Mutant sample 2” and DRG from two control littermates were dissected and assigned as “Control sample 2.”