title: A homolog of Drosophila grainy head is essential for epidermal integrity in mice.
abstract: The Drosophila cuticle is essential for maintaining the surface barrier defenses of the fly. Integral to cuticle resilience is the transcription factor grainy head, which regulates production of the enzyme required for covalent cross-linking of the cuticular structural components. We report that formation and maintenance of the epidermal barrier in mice are dependent on a mammalian homolog of grainy head, Grainy head-like 3. Mice lacking this factor display defective skin barrier function and deficient wound repair, accompanied by reduced expression of transglutaminase 1, the key enzyme involved in cross-linking the structural components of the superficial epidermis. These findings suggest that the functional mechanisms involving protein cross-linking that maintain the epidermal barrier and induce tissue repair are conserved across 700 million years of evolution.
authors.affiliation: Rotary Bone Marrow Research Laboratories, c/o Royal Melbourne Hospital Post Office, Grattan Street, Parkville, Victoria, Australia 3050.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Ting
authors.forename: Jacinta
authors.initials: J
authors.lastname: Caddy
authors.forename: Nikki
authors.initials: N
authors.lastname: Hislop
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wilanowski
authors.forename: Alana
authors.initials: A
authors.lastname: Auden
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Zhao
authors.forename: Sarah
authors.initials: S
authors.lastname: Ellis
authors.forename: Pritinder
authors.initials: P
authors.lastname: Kaur
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Uchida
authors.forename: Walter M
authors.initials: WM
authors.lastname: Holleran
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
authors.forename: John M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Jane
mesh_terms: D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian / Q000502:physiology; D047108:Embryonic Development; D004817:Epidermis / Q000196:embryology* / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D015870:Gene Expression; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D009154:Mutation; D010539:Permeability; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C499942:Grhl3 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; D011503:Transglutaminases; C105804:transglutaminase 1