Epidermal Wnt controls hair follicle induction by orchestrating dynamic signaling crosstalk between the epidermis and dermis

J Invest Dermatol. 2013 Apr;133(4):890-8. doi: 10.1038/jid.2012.407. Epub 2012 Nov 29.

Abstract

A signal first arising in the dermis to initiate the development of hair follicles has been described for many decades. Wnt is the earliest signal known to be intimately involved in hair follicle induction. However, it is not clear whether the inductive signal of Wnt arises intradermally or intraepidermally. Whether Wnt acts as the first dermal signal to initiate hair follicle development also remains unclear. Here we report that Wnt production mediated by Gpr177, the mouse Wls ortholog, is essential for hair follicle induction. Gpr177, encoding a multipass transmembrane protein, regulates Wnt sorting and secretion. Cell type-specific abrogation of the signal reveals that only epidermal, but not dermal, production of Wnt is required. An intraepidermal Wnt signal is necessary and sufficient for hair follicle initiation. However, the subsequent development depends on reciprocal signaling crosstalk of epidermal and dermal cells. Wnt signals within the epidermis and dermis and crossing between the epidermis and dermis have distinct roles and specific functions in skin development. This study not only defines the cell type responsible for Wnt production, but also reveals a highly dynamic regulation of Wnt signaling at different steps of hair follicle morphogenesis. Our findings uncover a mechanism underlying hair follicle development orchestrated by the Wnt pathway.

Publication types

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

MeSH terms

  • Animals
  • Cell Communication / physiology*
  • Dermis / cytology*
  • Dermis / embryology
  • Dermis / physiology
  • Epidermal Cells*
  • Epidermis / embryology
  • Epidermis / physiology
  • Gene Expression Regulation, Developmental / physiology
  • Hair Follicle / cytology*
  • Hair Follicle / physiology
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / physiology*
  • Wnt2 Protein / metabolism
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, mouse
  • Gpr177 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Wnt Proteins
  • Wnt10a protein, mouse
  • Wnt10b protein, mouse
  • Wnt2 Protein
  • Wnt7b protein, mouse
  • beta Catenin