View the Current Issue

Article

  • The EMBO Journal (2008) 27, 886 - 897
  • doi:10.1038/emboj.2008.24

Published online: 21 February 2008

Perturbed desmosomal cadherin expression in grainy head-like 1-null mice

Tomasz Wilanowski1, Jacinta Caddy1, Stephen B Ting1, Nikki R Hislop1, Loretta Cerruti1, Alana Auden1, Lin-Lin Zhao1, Stephen Asquith2, Sarah Ellis2, Rodney Sinclair3, John M Cunningham4 and Stephen M Jane1,5

  1. Rotary Bone Marrow Research Laboratories, Melbourne Health Research Directorate, Royal Melbourne Hospital, Parkville, Victoria, Australia
  2. Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
  3. Department of Dermatology, St Vincent's Hospital, Fitzroy, Victoria, Australia
  4. Department of Pediatrics and Institute of Molecular Pediatric Sciences, University of Chicago, Chicago, IL, USA
  5. Department of Medicine, University of Melbourne, Parkville, Victoria, Australia

Correspondence to:

Stephen M Jane, Rotary Bone Marrow Research Laboratories, Melbourne Health Research Directorate, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia. Tel.: +61 3 93428641; Fax: +61 3 93428634; E-mail: jane@wehi.edu.au

Received 22 July 2007; Accepted 31 January 2008

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.

  • Keywords:

    • cadherins,
    • desmoglein,
    • epidermis,
    • grainy head,
    • hair