The role of Eda signalling in salivary gland development

Hypohidrotic ectodermal dysplasia (HED) is a disorder characterized by defective ectodermal organ development. This includes the salivary glands (SG), which have an important role in lubricating the oral cavity. In humans and mice, HED is caused by mutations in EDA pathway genes, the most common form of HED being caused by defects in the ligand EDA. The mouse mutant Tabby ( Ta ) lacks Eda and is an excellent model for the study of human HED. It has been shown that aspects of the Ta HED phenotype can be rescued by maternal injection or in vitro culture supplementation with recombinant EDA, with the rescue being dependent on concentration and developmental timing of EDA administration. This work aims to characterize the embryonic Ta SG phenotype and attempt rescue of the glands by EDA supplementation in vitro , with a focus on establishing the timing and concentration of EDA required to achieve rescue. We show that Ta submandibular glands (SMGs) are hypoplastic with reduced epithelial branching at E15. However Ta SMGs appear normal at E13.5. Furthermore, minor SGs in the Ta adult are reduced in number. Supplementation of E13.5 Ta SMGs in vitro with 0.5 æg/mL EDA partially rescues the branching phenotype, but rescue was not achieved with lower concentrations of EDA or with E15.5 and E17.5 SMGs. This work suggests that the SGs of HED patients could be rescued with EDA treatment, but that EDA would have to be administered early in development at a defined concentration for SG rescue to be successful.