Diversification and specialization of touch receptors in skin

Abstract

Our skin is the furthest outpost of the nervous system and a primary sensor for harmful and innocuous external stimuli. As a multifunctional sensory organ, the skin manifests a diverse and highly specialized array of mechanosensitive neurons with complex terminals, or end organs, which are able to discriminate different sensory stimuli and encode this information for appropriate central processing. Historically, the basis for this diversity of sensory specializations has been poorly understood. In addition, the relationship between cutaneous mechanosensory afferents and resident skin cells, including keratinocytes, Merkel cells, and Schwann cells, during the development and function of tactile receptors has been poorly defined. In this article, we will discuss conserved tactile end organs in the epidermis and hair follicles, with a focus on recent advances in our understanding that have emerged from studies of mouse hairy skin.

Figure 1.

Touch receptors of hairy skin. A diverse group of mechanosensory afferents innervate the hairy skin of mammals. The schematic depicts anatomically distinct end organs (right), which give rise to neural signals with distinct patterns of activity (center). These different classes of sensory neurons initiate the perception of different cutaneous sensations (left). Aβ afferents (blue shades), which have thick myelin sheaths, are gentle-touch receptors that display rapidly adapting (RA) or slowly adapting (SA) responses to touch. In hairy skin, RA afferents form lanecolate endings around hair follicles. Slowly adapting type I (SAI) afferents innervate Merkel cells (yellow) clustered in touch domes. Aδ afferents (green shades), which have thin myelin sheaths, include Aδ low-threshold mechanoreceptors (LTMRs) and A-mechanonociceptors (AM), whose morphological end organs have not been identified. C-afferents (magenta shades) include C-LTMRs that innervate hair follicles as well as pruritoceptors and nociceptors that innervate the epidermis. (Modified from Bautista and Lumpkin 2011.)

Figure 2.

Position and structure of touch domes in mice. (A) Overhead view schematic illustrates that touch domes (TDs) are asymmetrical crescent-shaped structures that are polarized to the caudal side of tylotrich (guard) hairs in the pelage skin. (B) Sagittal view schematic illustrating the key cellular and structural elements of the touch dome including unusual columnar keratinocytes juxtaposed with mature Merkel cells, which are innervated by SAI sensory afferents.

Figure 3.

Schematic representation of the structural components of the piloneural collar mechanoreceptor. Sensory projections from dorsal root ganglion neurons innervate the isthmus/upper bulge region of hair follicles in the pelage skin in circumferential (CF) and longitudinal (LF) patterns. The terminal endings of these sensory afferents are tightly associated with the upward processes of terminal Schwann cells (tSCs; red). Both the fibers and tIISC processes are associated with the outer root sheath keratinocytes in the hair follicle. The four types of pelage follicles, zigzag, awl, auchene, and guard, and the accompanying afferent combinations are shown. Bg, bulge; CF, circumferential fibers; IFE, interfollicular epidermis; Is, isthmus; LF, lanceolate fibers; SG, sebaceous gland.