title: Keratin 79 identifies a novel population of migratory epithelial cells that initiates hair canal morphogenesis and regeneration.
abstract: The formation of epithelial tubes underlies the development of diverse organs. In the skin, hair follicles resemble tube-like structures with lumens that are generated through poorly understood cellular rearrangements. Here, we show that creation of the hair follicle lumen is mediated by early outward movement of keratinocytes from within the cores of developing hair buds. These migratory keratinocytes express keratin 79 (K79) and stream out of the hair germ and into the epidermis prior to lumen formation in the embryo. Remarkably, this process is recapitulated during hair regeneration in the adult mouse, when K79(+) cells migrate out of the reactivated secondary hair germ prior to formation of a new hair canal. During homeostasis, K79(+) cells line the hair follicle infundibulum, a domain we show to be multilayered, biochemically distinct and maintained by Lrig1(+) stem cell-derived progeny. Upward movement of these cells sustains the infundibulum, while perturbation of this domain during acne progression is often accompanied by loss of K79. Our findings uncover previously unappreciated long-distance cell movements throughout the life cycle of the hair follicle, and suggest a novel mechanism by which the follicle generates its hollow core through outward cell migration.
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Veniaminova
authors.forename: Alicia N
authors.initials: AN
authors.lastname: Vagnozzi
authors.forename: Daniel
authors.initials: D
authors.lastname: Kopinke
authors.forename: Thy Thy
authors.initials: TT
authors.lastname: Do
authors.forename: L Charles
authors.initials: LC
authors.lastname: Murtaugh
authors.forename: Ivan
authors.initials: I
authors.lastname: Maillard
authors.forename: Andrzej A
authors.initials: AA
authors.lastname: Dlugosz
authors.forename: Jeremy F
authors.initials: JF
authors.lastname: Reiter
authors.forename: Sunny Y
authors.initials: SY
authors.lastname: Wong
mesh_terms: D000152:Acne Vulgaris / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D057809:HEK293 Cells; D006197:Hair / Q000196:embryology; D018859:Hair Follicle / Q000196:embryology* / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007633:Keratins / Q000235:genetics / Q000378:metabolism*; D053564:Keratins, Hair-Specific; D053531:Keratins, Type II; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012038:Regeneration
chemical_list: C507604:KRT85 protein, human; D053564:Keratins, Hair-Specific; D053531:Keratins, Type II; C586305:Krt79 protein, human; C101671:Lrig1 protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C586304:keratin 79, mouse; D007633:Keratins
keywords: Epithelial stem cells; Hair follicle; Infundibulum; Krt79; Lumen; Tube morphogenesis