Letter | Published:

Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors

Nature volume 509, pages 617621 (29 May 2014) | Download Citation



Touch submodalities, such as flutter and pressure, are mediated by somatosensory afferents whose terminal specializations extract tactile features and encode them as action potential trains with unique activity patterns1. Whether non-neuronal cells tune touch receptors through active or passive mechanisms is debated. Terminal specializations are thought to function as passive mechanical filters analogous to the cochlea’s basilar membrane, which deconstructs complex sounds into tones that are transduced by mechanosensory hair cells. The model that cutaneous specializations are merely passive has been recently challenged because epidermal cells express sensory ion channels and neurotransmitters2,3; however, direct evidence that epidermal cells excite tactile afferents is lacking. Epidermal Merkel cells display features of sensory receptor cells4,5 and make ‘synapse-like’ contacts5,6 with slowly adapting type I (SAI) afferents7,8,9. These complexes, which encode spatial features such as edges and texture1, localize to skin regions with high tactile acuity, including whisker follicles, fingertips and touch domes. Here we show that Merkel cells actively participate in touch reception in mice. Merkel cells display fast, touch-evoked mechanotransduction currents. Optogenetic approaches in intact skin show that Merkel cells are both necessary and sufficient for sustained action-potential firing in tactile afferents. Recordings from touch-dome afferents lacking Merkel cells demonstrate that Merkel cells confer high-frequency responses to dynamic stimuli and enable sustained firing. These data are the first, to our knowledge, to directly demonstrate a functional, excitatory connection between epidermal cells and sensory neurons. Together, these findings indicate that Merkel cells actively tune mechanosensory responses to facilitate high spatio-temporal acuity. Moreover, our results indicate a division of labour in the Merkel cell–neurite complex: Merkel cells signal static stimuli, such as pressure, whereas sensory afferents transduce dynamic stimuli, such as moving gratings. Thus, the Merkel cell–neurite complex is an unique sensory structure composed of two different receptor cell types specialized for distinct elements of discriminative touch.

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Thanks to R. Axel, A. MacDermott and the Lumpkin laboratory for helpful discussions and to D. Florez and R. Piskorowski for advice on whole-cell recordings. Funding was provided by NIH/NIAMS grants R01AR051219 and R21AR062307 (to E.A.L.), R01DE022358 (to A.P.) and fellowships to S.M. (5T32HL087745-05 and NIH/NINDS F32NS080544), M.N. (JSPS Research Fellowships for Young Scientists 24-7585), and A.M.N. (McNair Foundation). Microscopy and flow cytometry was performed with core support from the Columbia SDRC (P30AR044535) and Cancer Center (P30CA013696). Initial studies were performed at Baylor College of Medicine with assistance from Flow Cytometry and Genetically Engineered Mouse Shared Resources (P30CA125123).

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Author notes

    • Srdjan Maksimovic
    • , Masashi Nakatani
    •  & Yoshichika Baba

    These authors contributed equally to this work.


  1. Department of Dermatology, Columbia University, New York, New York 10032, USA

    • Srdjan Maksimovic
    • , Masashi Nakatani
    • , Yoshichika Baba
    • , Aislyn M. Nelson
    • , Kara L. Marshall
    •  & Ellen A. Lumpkin
  2. Graduate School of System Design and Management, Keio University, Yokohama 223-8526, Japan

    • Masashi Nakatani
  3. Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77006, USA

    • Aislyn M. Nelson
    • , Scott A. Wellnitz
    •  & Pervez Firozi
  4. Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla California 92037, USA

    • Seung-Hyun Woo
    • , Sanjeev Ranade
    •  & Ardem Patapoutian
  5. Department of Physiology & Cellular Biophysics, Columbia University, New York, New York 10032, USA

    • Ellen A. Lumpkin
  6. Program in Neurobiology & Behavior, Columbia University, New York, New York 10032, USA

    • Ellen A. Lumpkin


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S.M. screened transgenic mouse lines, and performed and analysed all ex vivo optogenetic experiments (Fig. 2 and Extended Data Figs 36). M.N. performed and analysed all whole-cell recordings (Fig. 1, Extended Data Fig. 1a, b and Extended Data Table 1). Y.B. performed and analysed recordings from Atoh1 and Piezo2 strains (Fig. 3, Extended Data Fig. 8 and Extended Data Table 2). A.M.N. performed qRT-PCR (Fig. 1i) and calcium imaging (Extended Data Fig. 1c–i). K.L.M. performed immunohistochemistry in Atoh1 strains (Extended Data Fig. 7) and assisted in preparation of all figures. S.A.W. and E.A.L. conceived optogenetic strategies. P.F. generated initial ChR2 transgenic mouse lines. E.A.L. conceived and supervised the project. During this manuscript’s peer-review process, we entered into a collaboration with S.H.W., S.R. and A.P., to analyse unpublished Piezo2CKO mice. S.R. generated Piezo2flox/flox mice and S.-H.W. generated and validated Krt14Cre;Piezo2flox/flox mice in the laboratory of A.P. The manuscript was written by S.M., M.N., Y.B. and E.A.L. and edited by A.M.N., K.L.M., S.A.W., P.F., S.-H.W. and A.P.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ellen A. Lumpkin.

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