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Science 308 (5720): 411-413

Copyright © 2005 by the American Association for the Advancement of Science

A Homolog of Drosophila grainy head Is Essential for Epidermal Integrity in Mice

Stephen B. Ting,1* Jacinta Caddy,1* Nikki Hislop,1 Tomasz Wilanowski,1 Alana Auden,1 Lin-lin Zhao,1 Sarah Ellis,2 Pritinder Kaur,3 Yoshikazu Uchida,4 Walter M. Holleran,4 Peter M. Elias,4 John M. Cunningham,5 Stephen M. Jane1{dagger}

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.

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.

{dagger} To whom correspondence should be addressed. E-mail: jane{at}

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