Skip to main content

Advertisement

You are viewing the new article page. Let us know what you think. Return to old version

Death domains, dysplasia and development

Edar is a member of the tumour-necrosis factor receptor (TNFR) family of signalling molecules that contains an intracellular death-domain. Mutation of the mammalian downless gene encoding Edar, or Tabby which encodes its ligand Eda, results in ectodermal dysplasia and defective morphogenesis. In the December 20/27 Nature, Headon et al. report characterization of the protein encoded by the mouse crinkled locus, a mutation in which results in hypohidrotic dysplasia identical to Tabby and downless mutants (Nature 2001, 414:913-916). They performed positional cloning of the crinkled (cr) gene from cr x Mus castaneous backcrosses. Comparison of the syntenic regions of the mouse and human genomes led to the identification of a gene encoding a death-domain adaptor protein, named EDARADD. The human EDARADD gene is mutated in patients with autosomal hypohidrotic ectodermal dysplasia. The Edaradd protein interacts with the intracellular domain of Edar and resulted in activation of the signalling NFκB pathway. The downless and crinkled mutations abolish Edar-Edaradd interaction. This study defines a linear death-receptor pathway with a critical role in mammalian development.

References

  1. 1.

    The TNF and TNF receptor superfamilies: integrating mammalian biology.

  2. 2.

    Nature, [http://www.nature.com]

Download references

Rights and permissions

Reprints and Permissions

About this article

Keywords

  • Critical Role
  • Human Genome
  • Signalling Molecule
  • Positional Cloning
  • Adaptor Protein