Requirement of zinc transporter ZIP10 for epidermal development: Implication of the ZIP10-p63 axis in epithelial homeostasis

Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):12243-12248. doi: 10.1073/pnas.1710726114. Epub 2017 Oct 23.


Skin tissues, in particular the epidermis, are severely affected by zinc deficiency. However, the zinc-mediated mechanisms that maintain the cells that form the epidermis have not been established. Here, we report that the zinc transporter ZIP10 is highly expressed in the outer root sheath of hair follicles and plays critical roles in epidermal development. We found that ZIP10 marked epidermal progenitor cell subsets and that ablating Zip10 caused significant epidermal hypoplasia accompanied by down-regulation of the transactivation of p63, a master regulator of epidermal progenitor cell proliferation and differentiation. Both ZIP10 and p63 are significantly increased during epidermal development, in which ZIP10-mediated zinc influx promotes p63 transactivation. Collectively, these results indicate that ZIP10 plays important roles in epidermal development via, at least in part, the ZIP10-zinc-p63 signaling axis, thereby highlighting the physiological significance of zinc regulation in the maintenance of skin epidermis.

Keywords: ZIP10; development; hair follicle; skin epidermis; zinc transporter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / metabolism
  • Cations, Divalent
  • Cell Differentiation
  • Cell Proliferation
  • Embryo, Mammalian
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Hair Follicle / growth & development
  • Hair Follicle / metabolism*
  • HeLa Cells
  • Homeostasis / genetics*
  • Humans
  • Ion Transport
  • Mice
  • Mice, Transgenic
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • Skin / cytology
  • Skin / growth & development
  • Skin / metabolism*
  • Tissue Culture Techniques
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Zinc / metabolism*


  • Cation Transport Proteins
  • Cations, Divalent
  • Lgr6 protein, mouse
  • Phosphoproteins
  • Receptors, G-Protein-Coupled
  • Trans-Activators
  • Trp63 protein, mouse
  • ZIP10 protein, mouse
  • Zinc