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PMID: 17116754 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Lipid defect underlies selective skin barrier impairment of an epidermal-specific deletion of Gata-3.

The Journal of cell biology ·Vol. 175 ·No. 4 ·2006-11-20 ·Pages 661-70

de Guzman Strong C, Wertz PW, Wang C, Yang F, Meltzer PS, Andl T, Millar SE, Ho IC, Pai SY, Segre JA

Abstract

Skin lies at the interface between the complex physiology of the body and the external environment. This essential epidermal barrier, composed of cornified proteins encased in lipids, prevents both water loss and entry of infectious or toxic substances. We uncover that the transcription factor GATA-3 is required to establish the epidermal barrier and survive in the ex utero environment. Analysis of Gata-3 mutant transcriptional profiles at three critical developmental stages identifies a specific defect in lipid biosynthesis and a delay in differentiation. Genomic analysis identifies highly conserved GATA-3 binding sites bound in vivo by GATA-3 in the first intron of the lipid acyltransferase gene AGPAT5. Skin from both Gata-3-/- and previously characterized barrier-deficient Kruppel-like factor 4-/- newborns up-regulate antimicrobial peptides, effectors of innate immunity. Comparison of these animal models illustrates how impairment of the skin barrier by two genetically distinct mechanisms leads to innate immune responses, as observed in the common human skin disorders psoriasis and atopic dermatitis.

MeSH Terms
Animals Animals, Newborn Base Sequence Binding Sites Cell Differentiation Cell Proliferation Embryo, Mammalian/embryology Embryonic Development Epidermis/abnormalities,embryology,physiopathology,ultrastructure Exons/genetics GATA3 Transcription Factor/deficiency,genetics,metabolism Gene Deletion Immunity, Innate/immunology Introns/genetics Keratin-13/metabolism Kruppel-Like Factor 4 Kruppel-Like Transcription Factors/genetics Lipid Metabolism Mice Molecular Sequence Data Protein Binding Skin Transplantation Transcription, Genetic
Chemicals
GATA3 Transcription Factor KLF4 protein, human Keratin-13 Klf4 protein, mouse Kruppel-Like Factor 4 Kruppel-Like Transcription Factors
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
de Guzman Strong Cristina
National Human Genome Research Institute and 2National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Wertz Philip W
Wang Chenwei
Yang Fan
Meltzer Paul S
Andl Thomas
Millar Sarah E
Ho I-Cheng
Pai Sung-Yun
Segre Julia A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200605057
Published
2006-11-20
Pages
661-70
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2064601
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1083/jcb.200605057 PMC Full Text View journal details
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