The specification and wiring of mammalian cutaneous low-threshold mechanoreceptors

Abstract

The mammalian cutaneous low-threshold mechanoreceptors (LTMRs) are a diverse set of primary somatosensory neurons that function to sense external mechanical force. Generally, LTMRs are composed of Aβ-LTMRs, Aδ-LTMRs, and C-LTMRs, which have distinct molecular, physiological, anatomical, and functional features. The specification and wiring of each type of mammalian cutaneous LTMRs is established during development by the interplay of transcription factors with trophic factor signalling. In this review, we summarize the cohort of extrinsic and intrinsic factors generating the complex mammalian cutaneous LTMR circuits that mediate our tactile sensations and behaviors. For further resources related to this article, please visit the WIREs website.

FIGURE 1

Illustration showing specification of different subtypes of mammalian cutaneous low-threshold mechanoreceptors (LTMRs). The major known genes that specify each subtype at different stages are shown here. The final column shows main molecular markers to identify each subtype of LTMR in adult mice. Instances where the developmental lineage or gene expression for a given population is unclear are indicated with dotted lines or question marks. Reference citations are shown at the upper left-hand corner of each panel.

FIGURE 2

Illustration showing molecular mechanisms that control peripheral and central terminal development of Aβ rapidly adapting-low-threshold mechanoreceptors (RA-LTMRs). Genes that are important for Aβ RA-LTMR development are indicated in the dorsal root ganglion (DRG) cell body. Signalling molecules that direct terminal development are indicated in the spinal cord and skin. In the epidermis, SB/SS = stratum basalis/stratum spinosum, SG = stratum granulosum, SC = stratum corneum.

FIGURE 3

Illustration showing molecular mechanisms that control peripheral terminal development of Aβ slowly adapting-low-threshold mechanoreceptors (SA-LTMRs). Genes that are important for Aβ SA-LTMR development are indicated in the dorsal root ganglion (DRG) cell body. Signalling molecules that direct terminal development are indicated in the skin.

FIGURE 4

Illustration showing molecular mechanisms that control peripheral and central terminal development of Aδ-low-threshold mechanoreceptors (LTMRs). Genes that are either are important for Aδ-LTMR development are indicated in the dorsal root ganglion (DRG) cell body. Signalling molecules that direct terminal development are indicated in the skin.

FIGURE 5

Illustration showing molecular mechanisms that control peripheral and central terminal development of C-low-threshold mechanoreceptors (LTMRs) and C tactile fibers. Genes that either specifically mark the C-LTMRs or C tactile fibers or are important for their development are indicated in the dorsal root ganglion (DRG) cell body. Signalling molecules that direct terminal development are indicated in the spinal cord and skin.