Article: article from journal or magazin.
Identification of ectodysplasin target genes reveals the involvement of chemokines in hair development.
Journal of Investigative Dermatology
Ectodysplasin (Eda), a member of the tumor necrosis factor (Tnf) family, regulates skin appendage morphogenesis via its receptor Edar and transcription factor NF-κB. In humans, inactivating mutations in the Eda pathway components lead to hypohidrotic ectodermal dysplasia (HED), a syndrome characterized by sparse hair, tooth abnormalities, and defects in several cutaneous glands. A corresponding phenotype is observed in Eda-null mice, where failure in the initiation of the first wave of hair follicle development is a hallmark of HED pathogenesis. In an attempt to discover immediate target genes of the Eda/NF-κB pathway, we performed microarray profiling of genes differentially expressed in embryonic skin explants after a short exposure to recombinant Fc-Eda protein. Upregulated genes included components of the Wnt, fibroblast growth factor, transforming growth factor-β, Tnf, and epidermal growth factor families, indicating that Eda modulates multiple signaling pathways implicated in skin appendage development. Surprisingly, we identified two ligands of the chemokine receptor cxcR3, cxcl10 and cxcl11, as new hair-specific transcriptional targets of Eda. Deficiency in cxcR3 resulted in decreased primary hair follicle density but otherwise normal hair development, indicating that chemokine signaling influences the patterning of primary hair placodes only.
Animals, Chemokine CXCL10/genetics, Chemokine CXCL10/metabolism, Chemokine CXCL11/genetics, Chemokine CXCL11/metabolism, Chemokines/metabolism, Disease Models, Animal, Ectodermal Dysplasia/genetics, Ectodermal Dysplasia/metabolism, Ectodysplasins/genetics, Ectodysplasins/metabolism, Hair/growth & development, Hair/metabolism, Hair Follicle/growth & development, Hair Follicle/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B/metabolism, Signal Transduction/physiology, Skin/metabolism, Tissue Culture Techniques
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