Merkel Cells Are Multimodal Sensory Cells: A Review of Study Methods

Abstract

Merkel cells (MCs) are rare multimodal epidermal sensory cells. Due to their interactions with slowly adapting type 1 (SA1) Aβ low-threshold mechanoreceptor (Aβ-LTMRs) afferents neurons to form Merkel complexes, they are considered to be part of the main tactile terminal organ involved in the light touch sensation. This function has been explored over time by ex vivo, in vivo, in vitro, and in silico approaches. Ex vivo studies have made it possible to characterize the topography, morphology, and cellular environment of these cells. The interactions of MCs with surrounding cells continue to be studied by ex vivo but also in vitro approaches. Indeed, in vitro models have improved the understanding of communication of MCs with other cells present in the skin at the cellular and molecular levels. As for in vivo methods, the sensory role of MC complexes can be demonstrated by observing physiological or pathological behavior after genetic modification in mouse models. In silico models are emerging and aim to elucidate the sensory coding mechanisms of these complexes. The different methods to study MC complexes presented in this review may allow the investigation of their involvement in other physiological and pathophysiological mechanisms, despite the difficulties in exploring these cells, in particular due to their rarity.

Keywords: Merkel cells; ex vivo; in silico; in vitro; in vivo.

Figure 1

Representative diagram of the different approaches allowing the study of cells that compose the Merkel complexes. The different study methods are in vitro, ex vivo, in vivo, and in silico. In each approach, the material and the techniques are different. They complement each other to identify new functions or characteristics attributed to Merkel complexes.

Figure 2

Merkel cell–neurite complexes. (A). Merkel cells associated with slowly adapting type 1 (SA1) Aβ-low-threshold mechanoreceptor (Aβ-LTMRs) afferents neurons form the Merkel complex. They are present within the basal layer of the epidermis in both hairy and glabrous skin. (B,C). A light mechanical stimulation applied to skin triggers action potentials in Aβ SAI-LTMRs, ultimately leading to light touch. Activation of PIEZO2, a mechanically activated ion channel, leads to the release of calcium in Merkel cells, which causes SA1 impulses to be triggered by Aβ afferent neurons. (D). Representative three-dimensional reconstruction of a Merkel complex in hairy rat skin. In the photograph, contact between an Aβ fiber (yellow) and a Merkel cell (red) can be observed. Merkel cells were immunoreactive to anti-cytokeratin 20 (red) and the Aβ fiber to anti-neurofilament 200 (yellow) (confocal laser scanning microscopy). Scale bar = 5 µm. (Created with BioRender.com.).