Activity-dependent development of the body's touch receptors

Santiago, C.; Sharma, N.; Africawala, N.; Siegrist, J.; Handler, A.; Tasnim, A.; Anjum, R.; Turecek, J.; Lehnert, B. P.; Renauld, S.; Nolan-Tamariz, M.; Iskols, M.; Magee, A. R.; Paradis, S.; Ginty, D. D.

doi:10.1101/2023.09.23.559109

bioRxiv · 10.1101/2023.09.23.559109

Activity-dependent development of the body's touch receptors

Santiago, C.·Sharma, N.·Africawala, N.·Siegrist, J.·Handler, A.·Tasnim, A.·Anjum, R.·Turecek, J.·Lehnert, B. P.·Renauld, S.·Nolan-Tamariz, M.·Iskols, M.·Magee, A. R.·Paradis, S.·Ginty, D. D.

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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 and altered somatosensory neuron central targeting. Single cell RNA sequencing of Piezo2 conditional mutants revealed changes in gene expression in the sensory neurons activated by light mechanical forces, whereas other neuronal classes were less affected. To further test the role of activity in mechanosensory end organ development, we genetically deleted the voltage-gated sodium channel Nav1.6 (Scn8a) in somatosensory neurons throughout development and found that Scn8a mutants also have disrupted somatosensory neuron morphologies and altered electrophysiological responses to mechanical stimuli. Together, these findings indicate that mechanically evoked neuronal activity acts early in life to shape the maturation of the mechanosensory end organs that underlie our sense of gentle touch.

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Santiago, C., Sharma, N., Africawala, N., Siegrist, J., Handler, A., Tasnim, A., Anjum, R., Turecek, J., Lehnert, B. P., Renauld, S., Nolan-Tamariz, M., Iskols, M., Magee, A. R., Paradis, S., Ginty, D. D.. 2023-09-24. Activity-dependent development of the body's touch receptors. https://doi.org/10.1101/2023.09.23.559109

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