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, teeth and hairs 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 (HE D). 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 this project is to further investigate the specific role of Edar signalling pathway in hair and tooth development, by finding its direct target genes and by placing it in the network of other signalling pathways already known. This project will be performed using the Affymetrix microarrays method. Mutant tabby mice, as well as generated transgenic mice will be used as experimental models.
This work will allow enhancing the current knowledge on signals and regulation pathways involved in the making of ectodermal organs. Moreover, this work will improve understanding of human syndromes such as HED, bring highlights on stem cells differentiation and tumourigenic process, and have concrete applications in regenerative biology.
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