Objectives:
Hypohidrotic ectodermal dysplasia is a syndrome characterized by defective development of ectodermal structures. In humans and mice the disorder is caused by mutations in the Eda pathway. Defects in Eda (the ligand) and Edar (the receptor) in the mouse lead to hypoplasia and dysplasia of developing salivary glands. However the role of Edaradd (the intracellular component) has not been investigated. The objective of this study was to describe the embryonic Submandibular gland (SMG) phenotype of Edaradd mutant mice and to determine the expression pattern of Edaradd in wild type SMGs.
Methods:
Edaradd mutant and wildtype mice were paraffin sectioned, and analysed for insitu hybridization and histology of submandibular gland development.
Results:
The SMGs of Edaradd mutant mice are hypoplastic in comparison to the wild type and exhibit disorganised epithelium with reduced branching and histodifferentiation. Edaradd was expressed in the epithelium of the wild type SMG from E13.5 onwards. Expression of Shh in the SMGs was downregulated in the Edaradd mutant in comparison to the wild type, while the expression of E-cad was unaffected.
Conclusion:
The SMG phenotype of Edaradd mutant mice is similar to that seen in Eda mutants, and the expression of Edaradd in the wild type mirrors that of Edar. This suggests that Edaradd is an essential component of the Eda pathway, interacting with Edar to regulate epithelial branching and differentiation in the SMGs. The downregulation of Shh in the SMGs of Edaradd mutants suggests that the Eda pathway acts through Shh to regulate SMG development.
This is the first work to characterize the SMG phenotype of Edaradd mutant mice and to examine the expression pattern of Edaradd in the SMGs.
This work is funded by the NFED and the MRC.