Lipid defect underlies selective skin barrier impairment of an epidermal-specific deletion of Gata-3
نویسندگان
چکیده
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.
منابع مشابه
Lipid defect underlies selective skin barrier impairment of an epidermal - specifi c deletion of Gata - 3 Cristina
Mammalian epidermis functions as a barrier to prevent both water loss to the terrestrial environment and entry of toxic and pathogenic agents into the organism (Elias, 2005; Segre, 2006). Embryonic ectoderm is specifi ed to an epidermal fate at murine embryonic day (E) 8.5, regulated by the p63 transcription factors (Koster and Roop, 2004). At E9.5, this single layer of basal cells express cyto...
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ورودعنوان ژورنال:
- The Journal of Cell Biology
دوره 175 شماره
صفحات -
تاریخ انتشار 2006