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Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7195-200. doi: 10.1073/pnas.1504177112. Epub 2015 May 26.

Neural Hedgehog signaling maintains stem cell renewal in the sensory touch dome epithelium.

Author information

1
Dermatology Branch, Center of Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
2
Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892;
3
Department of Molecular, Cell and Development Biology, University of California, Santa Cruz, CA 95064;
4
Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065; Biochemistry and Structural Biology, Cell and Developmental Biology, and Molecular Biology (BCMB) Graduate Program, Weill Cornell Medical School, New York, NY 10065.
5
Dermatology Branch, Center of Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; isaac.brownell@nih.gov.

Abstract

The touch dome is a highly patterned mechanosensory structure in the epidermis composed of specialized keratinocytes in juxtaposition with innervated Merkel cells. The touch dome epithelium is maintained by tissue-specific stem cells, but the signals that regulate the touch dome are not known. We identify touch dome stem cells that are unique among epidermal cells in their activated Hedgehog signaling and ability to maintain the touch dome as a distinct lineage compartment. Skin denervation reveals that renewal of touch dome stem cells requires a perineural microenvironment, and deleting Sonic hedgehog (Shh) in neurons or Smoothened in the epidermis demonstrates that Shh is an essential niche factor that maintains touch dome stem cells. Up-regulation of Hedgehog signaling results in neoplastic expansion of touch dome keratinocytes but no Merkel cell neoplasia. These findings demonstrate that nerve-derived Shh is a critical regulator of lineage-specific stem cells that maintain specialized sensory compartments in the epidermis.

KEYWORDS:

Hedgehog; Merkel cell; perineural niche; stem cell; touch dome

PMID:
26015562
PMCID:
PMC4466733
DOI:
10.1073/pnas.1504177112
[Indexed for MEDLINE]
Free PMC Article

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