ectodysplasinA

Ectodysplasin-A (EDA) is a member of the tumor necrosis factor (TNF) ligand family encoded by the EDA gene on the X chromosome. It is produced as a transmembrane precursor that can be cleaved to release soluble ligands, notably ectodysplasin-A1 (EDA-A1); a shorter isoform, EDA-A2, is produced by alternative splicing and has a less clearly defined role.

EDA-A1 binds to the EDAR receptor (ectodysplasin-A receptor), forming a receptor-adaptor complex with EDARADD and activating the NF-κB signaling pathway. This signaling pathway regulates the development of ectodermal derivatives, including skin appendages. The interaction is critical for the proper formation of structures such as hair follicles, teeth, and sweat glands.

Mutations in EDA cause X-linked hypohidrotic ectodermal dysplasia (XLHED), a condition characterized by reduced or absent sweat glands (hypohidrosis/anhidrosis), missing or malformed teeth (hypodontia or conical teeth), and sparse hair (hypotrichosis). The phenotype can vary in severity, and female carriers may display milder features.

EDA is part of a broader group of ectodermal dysplasias. Autosomal forms of ectodermal dysplasia involve other components of the same signaling axis, including EDAR, EDARADD, and, in some cases, WNT10A. The Tabby mouse model, carrying an Eda mutation, recapitulates many human features and has been instrumental in studying the pathway.

In research, the EDA-EDAR-NF-κB signaling axis remains a focus for exploring potential therapies, with preclinical studies investigating replacement or activation of EDA-A1 to restore ectodermal development in affected models.