Touch dome, a specialized epidermal structure comprised from mechanosensory Merkel cell-neurite complex, has been known to change their numbers in the spontaneous hair cycle in mice. At the anagen phase, the number of Merkel cells are dramatically reduced with the loss of terminal neurites in touch dome afferents, indicating neuronal plasticity in healthy skin during hair-follicle regeneration. In this study, we focused on the role of Merkel cell-neurite complex in hair growth on the basis of the reports that the mechanical stimulation of human scalp by a massage improves hair thickness. To investigate the molecular mechanisms of reciprocal signaling interactions between the nerve fibers and innervated Merkel cells, two kinds of Merkel cell-neurite complex in vitro models were generated using a human Merkel cell carcinoma cell line (MCC14/2) and rat dorsal root ganglion (DRG) neurons. As the first in vitro model, we examined whether secreted factors from MCC14/2 cells regulated DRG neuronal behavior. Application of compression force using a gas-pressurized culture chamber, as a model of gentle touch stimuli, led to an induction of c-Fos, accompanied by the upregulation of the chemorepellent Draxin in MCC14/2 cells. When the conditioned media derived from compression force-treated MCC14/2 cells applied to DRG neurons, the chemorepulsive activity was observed via a PI3K/AKT-dependent manner. As the second in vitro model, we tried to generate Merkel cell-neurite complex using an axon investigation system (AXIS), which can isolate nerve fibers from cell bodies. DRG neurite-MCC14/2 cell cocultures allowed to form synaptic contacts with MCC14/2 cells, as determined by synaptophysin immunoreactivity. These results suggest that the models are useful tools to provide in vivo correlated information for understanding the molecular mechanism and evaluating new targeted therapies of hair growth.

ESDR329 - In vitro co-culture models of merkel cell-neurite complex in touch domes

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING