The cellular basis of mechanosensory Merkel-cell innervation during development

Elife. 2019 Feb 22:8:e42633. doi: 10.7554/eLife.42633.

Abstract

Touch sensation is initiated by mechanosensory neurons that innervate distinct skin structures; however, little is known about how these neurons are patterned during mammalian skin development. We explored the cellular basis of touch-receptor patterning in mouse touch domes, which contain mechanosensory Merkel cell-neurite complexes and abut primary hair follicles. At embryonic stage 16.5 (E16.5), touch domes emerge as patches of Merkel cells and keratinocytes clustered with a previously unsuspected population of Bmp4-expressing dermal cells. Epidermal Noggin overexpression at E14.5 disrupted touch-dome formation but not hair-follicle specification, demonstrating a temporally distinct requirement for BMP signaling in placode-derived structures. Surprisingly, two neuronal populations preferentially targeted touch domes during development but only one persisted in mature touch domes. Finally, Keratin-17-expressing keratinocytes but not Merkel cells were necessary to establish innervation patterns during development. These findings identify key cell types and signaling pathways required for targeting Merkel-cell afferents to discrete mechanosensory compartments.

Keywords: developmental biology; dorsal root ganglion; hair follicle; mechanoreceptor; mouse; neuroscience; skin; somatosensory neuron; touch.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning*
  • Bone Morphogenetic Protein 4 / analysis
  • Epidermal Cells / physiology
  • Keratinocytes / physiology
  • Keratins / analysis
  • Merkel Cells / physiology*
  • Mice
  • Peripheral Nerves / embryology*
  • Skin / embryology*

Substances

  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Krt17 protein, mouse
  • Keratins