Merkel Cells and Touch Sensations
Merkel cells
The skin epithelium is an essential barrier that protects the body from the environment, helps to maintain temperature and keep water within the body, and performs sensory functions. These activities are largely provided by the epidermis, hair follicles, and specialized cells, including Merkel cells, which respectively serve protective barrier functions, provide thermoprotection, and are involved in mechanosensation. These mechanosensory cells are innervated by afferent neurons and are responsible for the tactile discrimination of the shape and texture of objects. Functional studies in mutant mice, in which Merkel cells were not formed, have demonstrated that the animals were unable to discriminate between different textures when performing behavioral tasks.
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Specification of Merkel cells during development
Most of our knowledge about Merkel cells comes from studies focused on the murine back skin, where these cells are found in specialized structures called touch domes which are located exclusively around primary hair follicles (Figure 1). Recently, we discovered that a subset of SOX9 expressing cells located inside of developing hair follicles are Merkel cell progenitors that give rise to Merkel cells at embryonic day (E) 14.5. We also found that fibroblast growth factor receptor 2 (FGFR2) plays an essential function in Merkel cell specification in the back skin, as loss of Fgfr2 leads to drastic decreases in the number of Merkel cells. While the specification of Merkel cells during embryogenesis is well studied, how these cells were maintained and regenerated in adulthood are still largely understudied.
In the lab, we sought to determine whether Merkel cells are renewable during mouse lifespan. We aim to uncover which cell populations contribute to Merkel cells regeneration and also which factors affect this process during normal homeostasis and upon wound healing.
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Merkel cell regeneration
The touch dome (TD) keratinocytes are specialized epidermal stem cells that intimately associate with the light touch sensing Merkel cells (MCs). Acting as a niche for MCs, TD keratinocytes facilitate and guide the establishment of neuronal innervation by Aβ low-threshold mechanoreceptors (Aβ-LTMRs) with MCs. MCs themselves are mechanosensitive cells that transduce light touch sensations in the skin. However, various physiological and skin condition models have shown a decrease in MCs within the epidermis. In our lab, we observed this reduction in a model of depilation-induced mild skin injury, where TD stem cells quickly regenerate MCs. Similarly, a decrease in MCs is noted in an experimental dry skin model, where MCs begin to transduce itch sensations in addition to their light touch functions. This phenomenon also appears in aged skin, where reduced MC numbers are also associated with increased itch. Our lab is interested in uncovering the mechanisms underlying the decrease and regeneration of MCs.
Touch dome, Merkel cells-niche, and pathological itch and pain
We are particularly intrigued by the complex, yet largely unexplored, niche of the touch dome. The interactions between stem cells, neurons, and mechanosensory MCs, along with various neuro-promotive extracellular matrix components, present a compelling area of study. Moreover, we want to understand how neuronal regulation of the touch dome influences its remodeling and its transition from sensing gentle touch to transducing pathological sensations like pain and itch, and how this happens on a cellular and genetic level. Previous studies and our observations suggest that nociceptive neuron fibers, such as C-fibers, may miswire with MCs, potentially activating these fibers to transduce itch and pain, while they signal through neuropeptide to control touch dome remodeling. Our lab is actively investigating the multiplex interactions among these diverse skin and neuronal cell types and how they govern sensory perception and remodeling.
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