TY - JOUR
T1 - FGF signalling controls the specification of hair placode-derived SOX9 positive progenitors to Merkel cells
AU - Nguyen, Minh Binh
AU - Cohen, Idan
AU - Kumar, Vinod
AU - Xu, Zijian
AU - Bar, Carmit
AU - Dauber-Decker, Katherine L.
AU - Tsai, Pai Chi
AU - Marangoni, Pauline
AU - Klein, Ophir D.
AU - Hsu, Ya Chieh
AU - Chen, Ting
AU - Mikkola, Marja L.
AU - Ezhkova, Elena
N1 - Funding Information:
For help, critical suggestions, reagents, and experimental input, we are grateful to Drs. Elaine Fuchs, Julie Segre, Michael Rendl, Chenleng Cai, Rui Yi, Sergei Ezhkov, and Carolina Perdigoto. We would like to thank Dr. Philippe Soriano for his generous gift of the Fgfr2 floxed and Fgfr2-mCherry mice. We also thank the personnel of the Microscope Facility at the Icahn School of Medicine at Mount Sinai and Light Microscopy Unit of the Institute of Biotechnology, University of Helsinki. C.B. is a Merksammer fund scholar. K. L.D.-D. was a trainee of the NIDCR-Interdisciplinary Training Program in Systems and Developmental Biology and Birth Defects T32HD075735. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award numbers R01 AR063724 (to E.E.) and in part by R01 AR070825 (to Y.-C.H.). This work was funded in part by NIH R35-DE026602 (to O.D.K.) and Sigrid Juselius Foundation and Academy of Finland (Grant no. 1272280) (to M.L.M.). We also thank for NCI P30 Cancer Center Support Grant (CCSG). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was funded in part by the Smith Family Awards Program, Basil O’Connor Starter Scholar Research Awards, and the Pew Scholar (to Y.-C.H.).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85048500895&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-04399-y
DO - 10.1038/s41467-018-04399-y
M3 - Article
C2 - 29899403
AN - SCOPUS:85048500895
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2333
ER -