EDAR TARGETS · Identification of Edar signalling pathway target genes

Final Activity Report Summary - EDAR TARGETS (Identification of Edar signalling pathway target genes)

In vertebrates, several organs including hairs, feathers, scales, nails, sweet and mammary glands develop as appendages of embryonic ectoderm. The development of these organs involves the action of common signalling molecules conserved from one species to the other. Especially, hairs and teeth form due to a cross-talk between epithelium and mesenchyme mediated by a network of common signalling molecules. A recently identified signalling pathway mediated by the ligand Eda-A1 and its receptor Edar has been shown to be involved in the initiation of hair and tooth development. Genetic studies revealed that genes of this pathway are inactivated in spontaneous mutant mice tabby and downless, as well as in a human disease named Hypohidrotic Ectodermal Dysplasia (HED). For these two species the malformation syndromes are characterised by both severe defects in hair formation, and missing and abnormally shaped teeth. The aim of the project was to further investigate the specific role of Edar signalling pathway in hair development, by finding its direct target genes and by placing it in the network of other signalling pathways already known. Ectodysplasin target genes were determined using the Affymetrix microarrays method. Mutant eda-/- (tabby) mice, as well as other transgenic mice were used as experimental models. We have found a list of 148 genes upregulated after ectodysplasin pathway stimulation in mouse skin, 22 of those being already produced within the first 1.5 hours of stimulation. Most of the best candidate genes studied were showing an expected expression pattern in developing hairs, but also in other ectodermal organs like tooth or mammary gland. We studied in more details the role of some of those genes in hair morphogenesis. We found that they were interacting with other signalling pathways already known as essential for ectodermal organ development. The results obtained were included in 2 peer-reviewed articles in international journals, one of them being currently under revision. This project has brought new insights on the role of ectodysplasin in ectodermal organ development, and has allowed to make the connection between other signalling pathways involved in this process. The results of our project might be useful in a long-term manner to design new medicins to rescue ectodermal organ development for patients suffering for ectodermal dysplasia.

Data: CORDIS, © European Union