Oral Biosciences & Medicine
Oral Biosci Med 1 (2004), No. 3     30. Sep. 2004
Oral Biosci Med 1 (2004), No. 3  (30.09.2004)

Page 195-206

Ectodysplasin-A1 Promotes Epithelial Branching and Duct Formation in Developing Submandibular Glands
Nordgarden, Hilde/Mustonen, Tuija/Berner, Heidi Sire/Pispa, Johanna/Ilmonen, Maritta/Jensen, Janicke Liaaen/Storhaug, Kari/Thesleff, Irma/Lyngstadaas, Staale Petter
The genes encoding ectodysplasin-A (ED1/Eda) are involved in development of ectodermal organs and their mutations cause human and murine X-linked ectodermal dysplasia, XLHED and Tabby, respectively. In the present study, the effects of absent Eda signalling on human salivary gland function, as well as absent and ectopic signalling of the splice form Eda-A1 on mouse submandibular gland (SMG) morphogenesis and transcription of selected signalling molecules were examined.
Ten male patients diagnosed with XLHED as well as ten age-matched male control persons were included in the study. These persons were extracted from a larger group of persons diagnosed with different forms of ectodermal dysplasias. All participants were examined with regard to unstimulated and chewing stimulated whole salivary flow and citric acid stimulated parotid and submandibular/sublingual flow.
The study demonstrated that salivary secretion is reduced in persons diagnosed with XLHED. Tabby SMGs were found to have few and small ductal structures, whereas SMGs in K14-Eda-A1 transgenic mice overexpressing the Eda splice form Eda-A1 were dysplastic with large ductal structures. Early SMGs of K14-Eda-A1 transgenic mice had more branches than wild type control explants, and this was still the case after 44 h in culture. Eda-A1 expression was observed in wild type SMG mesenchyme and in both mesenchyme and epithelium in K14-Eda-A1 transgenic SMGs. Eda-A1 clearly promoted the formation of the luminal epithelium expressing Tsc-22.
These findings indicate that Eda-A1 has important functions during both human and murine salivary gland development.

Keywords: Ectodysplasin-A1, X-linked hypohidrotic ectodermal dysplasia, Tabby, submandibular gland, Edar, TSC-22