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A Homolog of Drosophila grainy head Is Essential for Epidermal Integrity in Mice
Stephen B. Ting,1*Jacinta Caddy,1*Nikki Hislop,1Tomasz Wilanowski,1Alana Auden,1Lin-lin Zhao,1Sarah Ellis,2Pritinder Kaur,3Yoshikazu Uchida,4Walter M. Holleran,4Peter M. Elias,4John M. Cunningham,5Stephen M. Jane1
The Drosophila cuticle is essential for maintaining the surfacebarrier defenses of the fly. Integral to cuticle resilienceis the transcription factor grainy head, which regulates productionof the enzyme required for covalent cross-linking of the cuticularstructural components. We report that formation and maintenanceof the epidermal barrier in mice are dependent on a mammalianhomolog of grainy head, Grainy head-like 3. Mice lacking thisfactor display defective skin barrier function and deficientwound repair, accompanied by reduced expression of transglutaminase1, the key enzyme involved in cross-linking the structural componentsof the superficial epidermis. These findings suggest that thefunctional mechanisms involving protein cross-linking that maintainthe epidermal barrier and induce tissue repair are conservedacross 700 million years of evolution.
1 Rotary Bone Marrow Research Laboratories, c/o Royal Melbourne Hospital Post Office, Grattan Street, Parkville, Victoria, Australia 3050. 2 Microscopy Imaging Facility, Peter MacCallum Research Institute, East Melbourne, Victoria, Australia 3001. 3 Epithelial Stem Cell Biology Laboratory, Peter MacCallum Research Institute, East Melbourne, Victoria, Australia 3001. 4 Dermatology Service and Research Unit, Department of Veterans Affairs Medical Center, and Department of Dermatology, School of Medicine, University of California, San Francisco, CA 94121, USA. 5 Division of Experimental Hematology, St. Jude Children's Research Hospital, Memphis, TN 38101, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: jane{at}wehi.edu.au
Genomic Survey of Candidate Stress-Response Genes in the Estuarine Anemone Nematostella vectensis.
A. M. Reitzel, J. C. Sullivan, N. Traylor-knowles, and J. R. Finnerty (2008)
Biol. Bull.
214, 233-254
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Grainy head promotes expression of septate junction proteins and influences epithelial morphogenesis.
M. Narasimha, A. Uv, A. Krejci, N. H. Brown, and S. J. Bray (2008)
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282, 33545-33552
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Increased expression of Grainyhead-like-3 rescues spina bifida in a folate-resistant mouse model.
P. Gustavsson, N. D.E. Greene, D. Lad, E. Pauws, S. C.P. de Castro, P. Stanier, and A. J. Copp (2007)
Hum. Mol. Genet.
16, 2640-2646
|Abstract »|Full Text »|PDF »
Grainyhead-related transcription factor is required for duct maturation in the salivary gland and the kidney of the mouse.
Y. Yamaguchi, S. Yonemura, and S. Takada (2006)
Development
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Inhibition of JNK Promotes Differentiation of Epidermal Keratinocytes.
A. Gazel, T. Banno, R. Walsh, and M. Blumenberg (2006)
J. Biol. Chem.
281, 20530-20541
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Lhx2 maintains stem cell character in hair follicles..
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