Identification of Ectodysplasin Target Genes Reveals the Involvement of Chemokines in Hair Development

The study identified that Ectodysplasin (Eda) regulated skin appendage morphogenesis through its receptor Edar and transcription factor NF-κB, with mutations in this pathway causing hypohidrotic ectodermal dysplasia (HED) characterized by sparse hair and other abnormalities. Using microarray profiling on embryonic skin explants exposed to recombinant Fc-Eda protein, researchers found that Eda influenced multiple signaling pathways, including Wnt, fibroblast growth factor, and Tnf. Notably, they discovered that chemokine ligands cxcl10 and cxcl11 were new hair-specific transcriptional targets of Eda. A deficiency in the chemokine receptor cxcR3 led to decreased primary hair follicle density, suggesting that chemokine signaling played a role in the patterning of primary hair placodes.