Journal Article

The structure and organization of lanceolate mechanosensory complexes at mouse hair follicles

Ginty, David D, Li, Lishi

2014

Overview

In mouse hairy skin, lanceolate complexes associated with three types of hair follicles, guard, awl/auchene and zigzag, serve as mechanosensory end organs. These structures are formed by unique combinations of low-threshold mechanoreceptors (LTMRs), Aβ RA-LTMRs, Aδ-LTMRs, and C-LTMRs, and their associated terminal Schwann cells (TSCs). In this study, we investigated the organization, ultrastructure, and maintenance of longitudinal lanceolate complexes at each hair follicle subtype. We found that TSC processes at hair follicles are tiled and that individual TSCs host axonal endings of more than one LTMR subtype. Electron microscopic analyses revealed unique ultrastructural features of lanceolate complexes that are proposed to underlie mechanotransduction. Moreover, Schwann cell ablation leads to loss of LTMR terminals at hair follicles while, in contrast, TSCs remain associated with hair follicles following skin denervation in adult mice and, remarkably, become re-associated with newly formed axons, indicating a TSC-dependence of lanceolate complex maintenance and regeneration in adults. Many mammals, such as cats, mice, and sea lions, have long whiskers that are particularly sensitive to touch. However, the hairs that cover the skin of most mammals are also important touch detectors. These hairs grow from follicles that are connected to the ends of the nerve cells that detect and convey touch information to the central nervous system. In mice, three main types of hair follicle—guard hairs, awl hairs, and zigzag hairs—are associated with combinations of three types of nerve endings. Much remains to be understood about how hair follicles and nerve cell endings—which are wrapped by cells called terminal Schwann cells—interact via structures called lanceolate complexes. Now, using a combination of genetics, microscopy and surgical procedures, Li and Ginty have studied these structures in unprecedented detail, and revealed some intriguing structural differences among the three types of hair follicles. Zigzag follicles—which make up the fur undercoat—are associated with fewer terminal Schwann cells than are awl follicles, whilst guard hair follicles have the most. High-resolution analyses revealed that distinct combinations of sensory nerve endings were associated with different types of hair follicle cells—which may underlie the unique responses of the different hair follicle types when the hairs are deflected. Furthermore, an individual terminal Schwann cell can be associated with more than one type of nerve ending, adding another layer of intricacy to the detection of hair movements. Killing the terminal Schwann cells in mice caused a complete loss of sensory nerve endings at hair follicles, which suggests that these cells are essential for maintaining the connection between the hair follicles and nerve cell endings. Interestingly, surgically removing nerve endings from the skin did not lead to a loss of terminal Schwann cells, and the nerve endings eventually grew back and reconnected with the hair follicles. In addition to shedding new light on the structures of lanceolate complexes in different types of hair follicles, the findings of Li and Ginty suggest that terminal Schwann cells maintain the nerve endings at hair follicles and guide their regeneration after damage. Uncovering the molecular mechanisms that control these processes represents an important next step in this research.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Ablation / Animals / Axons / Cell Death / Denervation / Diphtheria Toxin - pharmacology / Ethanol / Follicles / Genotype / Hair / hair follicle / Hair Follicle - drug effects / Hair Follicle - innervation / Hair Follicle - ultrastructure / Hair loss / lanceolate complex / low-threshold mechanoreceptor / Mechanoreceptors / Mechanoreceptors - drug effects / Mechanoreceptors - metabolism / Mechanoreceptors - ultrastructure / Mechanotransduction / Mechanotransduction, Cellular / Mice / Mice, Transgenic / Microscopy, Electron, Transmission / Morphogenesis / Nerve Regeneration / Neuroscience / Neurosciences / Phenotype / Schwann cells / Schwann Cells - drug effects / Schwann Cells - metabolism / Schwann Cells - ultrastructure / Skin / Tamoxifen - analogs & derivatives / Tamoxifen - pharmacology / terminal Schwann cell / Ultrastructure