Browsing by Subject "nystermä"

Lack of Ectodysplasin (EDA), caused by a mutated Eda gene, leads to a syndrome called hypohidrotic ectodermal dysplasia (XLHED) with defects in ectodermal organs such as teeth, hair and sweat glands. The molar teeth of Eda knock out (Eda KO) mice are absolutely and relatively smaller and have fewer cusps than the wild type (WT) molar teeth. In the absence of the EDA protein, the receptor of the EDA signalling pathway (EDAR) remains functional, and therefore EDA-protein therapy can rescue the development of ectodermal organs. The aim of this study was to determine EDA sensitivity windows and to describe the Edar expression pattern in developing mouse lower molars. Eda KO mouse skulls treated with EDA for 24 hours at different stages of development were imaged using x-ray microtomography. The response was studied by analysing the cusp patterns and size proportions of lower molars. In situ hybridisation was used to detect the Edar expression in the developing Eda KO and WT molars at different stages. The results show that molars are sensitive to EDA at the early stages of crown patterning, at the time when Edar is expressed in the primary enamel knot and the secondary enamel knots. The Edar expression pattern suggests that EDA signalling regulates molar size and cusp development through these signalling centres. EDA-treatment during a sensitivity window enhances the growth of the EDA sensitive molar, thereby breaking the previously reported inhibitory cascade –rule. The results of this study provide information for optimising the EDA therapy for XLHED patients.