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Perturbed desmosomal cadherin expression in grainy head‐like 1‐null mice
Author(s) -
Wilanowski Tomasz,
Caddy Jacinta,
Ting Stephen B,
Hislop Nikki R,
Cerruti Loretta,
Auden Alana,
Zhao LinLin,
Asquith Stephen,
Ellis Sarah,
Sinclair Rodney,
Cunningham John M,
Jane Stephen M
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.24
Subject(s) - biology , cadherin , microbiology and biotechnology , expression (computer science) , head (geology) , genetics , cell , paleontology , computer science , programming language
In Drosophila , the grainy head ( grh ) gene plays a range of key developmental roles through the regulation of members of the cadherin gene family. We now report that mice lacking the grh homologue grainy head‐like 1 ( Grhl1 ) exhibit hair and skin phenotypes consistent with a reduction in expression of the genes encoding the desmosomal cadherin, desmoglein 1 ( Dsg1 ). Grhl1 ‐null mice show an initial delay in coat growth, and older mice exhibit hair loss as a result of poor anchoring of the hair shaft in the follicle. The mice also develop palmoplantar keratoderma, analogous to humans with DSG1 mutations. Sequence analysis, DNA binding, and chromatin immunoprecipitation experiments demonstrate that the human and mouse Dsg1 promoters are direct targets of GRHL1. Ultrastructural analysis reveals reduced numbers of abnormal desmosomes in the interfollicular epidermis. These findings establish GRHL1 as an important regulator of the Dsg1 genes in the context of hair anchorage and epidermal differentiation, and suggest that cadherin family genes are key targets of the grainy head‐like genes across 700 million years of evolution.