Skin type-dependent development of specialized mechanosensory neurons

Abstract

Tactile sensation is mediated by low-threshold mechanoreceptors (LTMRs), which can exhibit highly distinct morphological and physiological properties depending on the skin type they innervate. Somatosensory neurons embryonically labeled with TrkB and Ret innervate glabrous (non-hairy) skin forming Meissner corpuscles, while in hairy skin, they form longitudinal lanceolate endings around hair follicles. How developing LTMRs acquire their unique properties in distinct skin types is unknown. Here, we report that structural specialization of hairy skin and glabrous skin LTMRs arises at nearly identical times during development. Interestingly, individual sensory neurons that terminate along the border of glabrous and hairy skin exhibit branches that form hair follicle lanceolate endings and others that form Meissner corpuscles. Using mouse mutants with ectopic glabrous skin on the dorsal paw, we found that LTMRs that innervate ectopic skin regions form endings in accordance with the altered skin type. Additionally, we report the transcriptional signatures of glabrous skin- and hairy skin-innervating TrkB+ and Ret+ neurons, which during development, largely overlap. Lastly, we characterize BMP5 as a skin-derived cue expressed specifically in glabrous skin but absent in hairy skin. Sensory neuron-specific deletion of the BMP type I receptor Bmpr1a led to strikingly aberrant Meissner corpuscles while hairy skin was intact. These findings indicate that embryonic LTMRs are able to form both Meissner corpuscles and lanceolate endings. It is the skin region that differentially instructs LTMRs to acquire skin type relevant structural properties during postnatal development, in part through BMP signaling. Thus, the specification of mechanosensory neuron features is flexibly determined by target tissues.