Skin-type-dependent development of murine mechanosensory neurons. Skin-type-dependent development of murine mechanosensory neurons

Mechanosensory neurons innervating the skin underlie our sense of touch. Fast-conducting, rapidly adapting mechanoreceptors innervating glabrous (non-hairy) skin form Meissner corpuscles, while in hairy skin, they associate with hair follicles, forming longitudinal lanceolate endings. How mechanoreceptors develop axonal endings appropriate for their skin targets is unknown. We report that mechanoreceptor morphologies across different skin regions are indistinguishable during early development but diverge post-natally, in parallel with skin maturation. Neurons terminating along the glabrous and hairy skin border exhibit hybrid morphologies, forming both Meissner corpuscles and lanceolate endings. Additionally, molecular profiles of neonatal glabrous and hairy skin-innervating neurons largely overlap. In mouse mutants with ectopic glabrous skin, mechanosensory neurons form end-organs appropriate for the altered skin type. Finally, BMP5 and BMP7 are enriched in glabrous skin, and signaling through type I bone morphogenetic protein (BMP) receptors in neurons is critical for Meissner corpuscle morphology. Thus, mechanoreceptor morphogenesis is flexibly instructed by target tissues. Overall design: Smart seq of glabrous and hairy skin innevating neurons

支配皮肤的机械感觉神经元是我们触觉感知的物质基础。快速传导、快速适应的机械感受器支配无毛（glabrous，非毛发覆盖）皮肤时，会形成迈斯纳小体（Meissner corpuscles）；而在有毛皮肤中，这类感受器会与毛囊结合，形成纵向柳叶状终末（longitudinal lanceolate endings）。目前学界尚未明确机械感受器如何形成适配其皮肤靶标的轴突终末。本研究发现，不同皮肤区域的机械感受器形态在发育早期并无显著差异，但在出生后会随皮肤成熟进程逐渐分化。位于无毛与有毛皮肤交界区域的神经元会呈现混合形态，可同时形成迈斯纳小体与柳叶状终末。此外，新生小鼠中支配无毛皮肤与有毛皮肤的神经元的分子表达谱存在高度重叠。在携带异位无毛皮肤的小鼠突变体中，机械感觉神经元会形成适配该异常皮肤类型的终末器官。最后，BMP5与BMP7在无毛皮肤中富集，神经元内I型骨形态发生蛋白（bone morphogenetic protein, BMP）受体介导的信号通路对迈斯纳小体的形态建成至关重要。综上，机械感受器的形态发生由靶组织灵活调控。实验整体设计：对支配无毛（glabrous）与有毛皮肤的神经元开展Smart-seq测序。