Skin-dependent morphological and molecular maturation of specialized mechanosensory neurons (S34.005)

Abstract

<h3>Objective:</h3> Identification of the developmental steps leading to somatosensory neuron development. <h3>Background:</h3> Our sense of touch is essential for life and relies on Low-Threshold Mechanoreceptors (LTMRs). LTMR subtypes characterized by early embryonic expression of Ntrk2 (TrkB) and Ret exhibit distinct properties depending on the skin region they innervate - hairy skin or glabrous(hairless) skin. In glabrous skin, TrkB+ and Ret+ LTMRs form Meissner corpuscles, while in hairy skin they form longitudinal lanceolate endings around hair follicles. These morphological features reflect the physiological properties and specialized functions of these neurons. The developmental steps leading to glabrous and hairy skin LTMR properties are largely unknown, in particular whether they are genetically pre-specified or whether interactions with different target skin regions define their unique features. <h3>Design/Methods:</h3> Sparse genetic labeling experiments demonstrate that morphological specialization of glabrous- and hairy paw skin-innervating TrkB+ and Ret+ LTMRs arise at nearly identical times during postnatal development. Interestingly, we find that individual neurons that terminate along the border of glabrous and hairy skin, termed “border neurons”, exhibit branches that form both lanceolate endings and Meissner corpuscle endings. Additionally, transcriptomic profiling and RNAscope experiments show that neonatal glabrous skin-and hairy skin-innervating TrkB+ and Ret+ neurons are transcriptionally similar, although distinct from other DRG neuron types. Lastly, using mouse mutants that have either ectopic glabrous skin or ectopic hairy skin we find that neurons that innervate ectopic skin regions of these mutants form ending types (either lanceolate or Meissner corpuscle endings) in accordance with the ectopic skin type. <h3>Results:</h3> These findings support a model in which embryonic TrkB+ and Ret+ LTMRs are able to form either Meissner corpuscle or lanceolate endings, and that the skin target region differentially instructs morphological maturation of these LTMR types. <h3>Conclusions:</h3> This model implies that neuronal identity in the peripheral nervous system is flexibly determined by target tissue. <b>Disclosure:</b> Dr. Koutsioumpa has nothing to disclose. Dr. Santiago has nothing to disclose. Miss Jacobs has nothing to disclose. Dr. Lehnert has received personal compensation for serving as an employee of Flagship Pioneering. Dr. Ginty has nothing to disclose.