A homolog of Drosophila grainy head is essential for epidermal integrity in mice.
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.
Ting
Stephen B
SB
Rotary Bone Marrow Research Laboratories, c/o Royal Melbourne Hospital Post Office, Grattan Street, Parkville, Victoria, Australia 3050.
Caddy
Jacinta
J
Hislop
Nikki
N
Wilanowski
Tomasz
T
Auden
Alana
A
Zhao
Lin-Lin
LL
Ellis
Sarah
S
Kaur
Pritinder
P
Uchida
Yoshikazu
Y
Holleran
Walter M
WM
Elias
Peter M
PM
Cunningham
John M
JM
Jane
Stephen M
SM
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*
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