FGF signalling controls the specification of hair placode-derived SOX9 positive progenitors to Merkel cells

Nat Commun. 2018 Jun 13;9(1):2333. doi: 10.1038/s41467-018-04399-y.

Abstract

Merkel cells are innervated mechanosensory cells responsible for light-touch sensations. In murine dorsal skin, Merkel cells are located in touch domes and found in the epidermis around primary hairs. While it has been shown that Merkel cells are skin epithelial cells, the progenitor cell population that gives rise to these cells is unknown. Here, we show that during embryogenesis, SOX9-positive (+) cells inside hair follicles, which were previously known to give rise to hair follicle stem cells (HFSCs) and cells of the hair follicle lineage, can also give rise to Merkel Cells. Interestingly, while SOX9 is critical for HFSC specification, it is dispensable for Merkel cell formation. Conversely, FGFR2 is required for Merkel cell formation but is dispensable for HFSCs. Together, our studies uncover SOX9(+) cells as precursors of Merkel cells and show the requirement for FGFR2-mediated epithelial signalling in Merkel cell specification.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Lineage
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism*
  • Female
  • Gene Knockout Techniques
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hair Follicle / cytology
  • Hair Follicle / embryology*
  • Hair Follicle / metabolism*
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • LIM-Homeodomain Proteins / metabolism
  • Male
  • Merkel Cells / cytology*
  • Merkel Cells / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Biological
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • Pregnancy
  • Receptor, Fibroblast Growth Factor, Type 2 / deficiency
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism*
  • SOX9 Transcription Factor / antagonists & inhibitors
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism

Substances

  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Hedgehog Proteins
  • LIM-Homeodomain Proteins
  • Lhx2 protein, mouse
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • SOX9 Transcription Factor
  • Shh protein, mouse
  • Sox9 protein, mouse
  • Transcription Factors
  • Green Fluorescent Proteins
  • Fgfr2 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 2