Santiago Celine, Sharma Nikhil, Africawala Nusrat, Siegrist Julianna, Handler Annie, Tasnim Aniqa, Anjum Rabia, Turecek Josef, Lehnert Brendan P, Renauld Sophia, Nolan-Tamariz Michael, Iskols Michael, Magee Alexandra R, Paradis Suzanne, Ginty David D
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, 02115, USA.
Department of Molecular Pharmacology and Therapeutics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
bioRxiv. 2023 Sep 25:2023.09.23.559109. doi: 10.1101/2023.09.23.559109.
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 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 Na1.6 () in somatosensory neurons throughout development and found that 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.
我们报告了活动在检测触觉的初级感觉神经元发育中的作用。躯体感觉神经元中的主要机械敏感离子通道Piezo2的基因缺失,导致机械感觉终末器官结构形成的深刻变化,并改变了躯体感觉神经元的中枢靶向。对条件性突变体进行单细胞RNA测序,揭示了由轻微机械力激活的感觉神经元中基因表达的变化,而其他神经元类别受影响较小。为了进一步测试活动在机械感觉终末器官发育中的作用,我们在整个发育过程中对躯体感觉神经元进行基因敲除电压门控钠通道Na1.6(),发现突变体也有躯体感觉神经元形态的破坏以及对机械刺激的电生理反应改变。这些发现共同表明,机械诱发的神经元活动在生命早期就发挥作用,塑造了构成我们轻触觉基础的机械感觉终末器官的成熟。