Spatiotemporal dynamics of sensory neuron and Merkel-cell remodeling are decoupled during epidermal homeostasis

As the juncture between the body and environment, epithelia are both protective barriers and sensory interfaces that continually renew. To determine whether sensory neurons remodel to maintain homeostasis, we used in vivo two-photon imaging of somatosensory axons innervating Merkel cells in adult mouse skin. These touch receptors were highly plastic: 63% of Merkel cells and 89% of branches appeared, disappeared, grew, regressed and/or relocated over a month. Interestingly, Merkel-cell plasticity was synchronized across arbors during rapid epithelial turnover. When Merkel cells remodeled, the degree of plasticity between Merkel-cell clusters and their axons was well correlated. Moreover, branches were stabilized by Merkel-cell contacts. These findings highlight the role of epithelial-neural crosstalk in homeostatic remodeling. Conversely, axons were also dynamic when Merkel cells were stable, indicating that intrinsic neural mechanisms drive branch plasticity. Two terminal morphologies innervated Merkel cells: transient swellings called boutons, and stable cups termed kylikes. In Atoh1 knockout mice that lack Merkel cells, axons showed higher complexity than control mice, with exuberant branching and no kylikes. Thus, Merkel cells limit axonal branching and promote branch maturation. Together, these results reveal a previously unsuspected high degree of plasticity in somatosensory axons that is biased, but not solely dictated, by plasticity of target epithelial cells. This system provides a platform to identify intrinsic and extrinsic mechanisms that govern axonal patterning in epithelial homeostasis. ### Competing Interest Statement The authors have declared no competing interest.