title: Gap junction development in the human fetal hair follicle and bulge region.
abstract: BACKGROUND
  Gap junctions, composed of connexin (Cx) subunits, are channels that allow intercellular communication between adjacent cells and are thought to play a key role in the regulation of cell proliferation and differentiation. The Cx expression pattern and formation of gap junctions in human fetal hair follicles has yet to be clarified, including the prominent follicular bulge region that is believed to be a site rich in stem cells.
  
  
  OBJECTIVE
  To study the expression of two major Cxs, Cx26 and Cx43, in developing hair follicles in skin samples from a series of human fetuses of estimated gestational age (EGA) 88-163 days, and to determine quantitatively the presence of gap junctions.
  
  
  METHODS
  We used immunofluorescence labelling to investigate the sequential expression pattern of Cx26 and Cx43 in developing human hair follicles. Gap junction formation was observed by electron microscopy and the numbers of gap junctions were analysed quantitatively. Results Both Cx26 and Cx43 expression were observed at 88 days' EGA in the inner part of the hair peg. At 135 days' EGA, Cx26 was expressed in the outer root sheath (ORS) and the inner root sheath (IRS), while Cx43 was expressed chiefly in the IRS, hair matrix and sebaceous glands. At 163 days' EGA, Cx26 expression was most intense in the outermost layer of the ORS, in contrast to Cx43 expression which was in the inner part of the ORS. In the bulge region, only Cx43 was expressed in a subset of cells in the bulge. Ultrastructurally, gap junctions were observed at 102 days' EGA in the hair peg, and the number of gap junctions increased as the hair follicle matured. Gap junctions were also observed between the bulge cells in considerable numbers.
  
  
  CONCLUSIONS
  The changing expression patterns of Cx26 and Cx43 and the increasing gap junction numbers suggest a close association of Cx expression and gap junction formation with hair follicle morphogenesis. In addition, the present ultrastructural observations demonstrate that considerable numbers of the bulge cells, a putative site rich in hair follicle stem cells, form gap junctions during human hair follicle development.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Arita
authors.forename: M
authors.initials: M
authors.lastname: Akiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuji
authors.forename: J R
authors.initials: JR
authors.lastname: McMillan
authors.forename: R A J
authors.initials: RA
authors.lastname: Eady
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D000072259:Connexin 26; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique / Q000379:methods; D017629:Gap Junctions / Q000502:physiology*; D005865:Gestational Age; D018859:Hair Follicle / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron / Q000379:methods
chemical_list: D018031:Connexin 43; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26