Open Access Open Badges Research

Large-scale identification of human genes implicated in epidermal barrier function

Eve Toulza1, Nicolas R Mattiuzzo1, Marie-Florence Galliano1, Nathalie Jonca1, Carole Dossat2, Daniel Jacob3, Antoine de Daruvar3, Patrick Wincker2, Guy Serre1 and Marina Guerrin1*

Author Affiliations

1 UMR 5165 "Epidermis Differentiation and Rheumatoid Autoimmunity", CNRS - Toulouse III University (IFR 30, INSERM - CNRS - Toulouse III University - CHU), allées Jules Guesde, 31073 Toulouse, France

2 Genoscope and CNRS UMR 8030, rue Gaston Crémieux, 91057 Evry, France

3 Centre de Bioinformatique Bordeaux, Université V. Segalen Bordeaux 2, rue Léo Saignat, 33076 Bordeaux Cedex, France

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Genome Biology 2007, 8:R107  doi:10.1186/gb-2007-8-6-r107

Published: 11 June 2007



During epidermal differentiation, keratinocytes progressing through the suprabasal layers undergo complex and tightly regulated biochemical modifications leading to cornification and desquamation. The last living cells, the granular keratinocytes (GKs), produce almost all of the proteins and lipids required for the protective barrier function before their programmed cell death gives rise to corneocytes. We present here the first analysis of the transcriptome of human GKs, purified from healthy epidermis by an original approach.


Using the ORESTES method, 22,585 expressed sequence tags (ESTs) were produced that matched 3,387 genes. Despite normalization provided by this method (mean 4.6 ORESTES per gene), some highly transcribed genes, including that encoding dermokine, were overrepresented. About 330 expressed genes displayed less than 100 ESTs in UniGene clusters and are most likely to be specific for GKs and potentially involved in barrier function. This hypothesis was tested by comparing the relative expression of 73 genes in the basal and granular layers of epidermis by quantitative RT-PCR. Among these, 33 were identified as new, highly specific markers of GKs, including those encoding a protease, protease inhibitors and proteins involved in lipid metabolism and transport. We identified filaggrin 2 (also called ifapsoriasin), a poorly characterized member of the epidermal differentiation complex, as well as three new lipase genes clustered with paralogous genes on chromosome 10q23.31. A new gene of unknown function, C1orf81, is specifically disrupted in the human genome by a frameshift mutation.


These data increase the present knowledge of genes responsible for the formation of the skin barrier and suggest new candidates for genodermatoses of unknown origin.