title: Recombinant EDA or Sonic Hedgehog rescue the branching defect in Ectodysplasin A pathway mutant salivary glands in vitro.
abstract: Hypohidrotic ectodermal dysplasia (HED) is characterized by defective ectodermal organ development. This includes the salivary glands (SGs), which have an important role in lubricating the oral cavity. In humans and mice, HED is caused by mutations in Ectodysplasin A (Eda) pathway genes. Various phenotypes of the mutant mouse Eda(Ta/Ta), which lacks the ligand Eda, can be rescued by maternal injection or in vitro culture supplementation with recombinant EDA. However, the response of the SGs to this treatment has not been investigated. Here, we show that the submandibular glands (SMGs) of Eda(Ta/Ta) mice exhibit impaired branching morphogenesis, and that supplementation of Eda(Ta/Ta) SMG explants with recombinant EDA rescues the defect. Supplementation of Edar(dlJ/dlJ) SMGs with recombinant Sonic hedgehog (Shh) also rescues the defect, whereas treatment with recombinant Fgf8 does not. This work is the first to test the ability of putative Eda target molecules to rescue Eda pathway mutant SMGs.
authors.affiliation: Department of Craniofacial Development, Dental Institute, King's College London, London, United Kingdom.
authors.forename: K L
authors.initials: KL
authors.lastname: Wells
authors.forename: C
authors.initials: C
authors.lastname: Mou
authors.forename: D J
authors.initials: DJ
authors.lastname: Headon
authors.forename: A S
authors.initials: AS
authors.lastname: Tucker
mesh_terms: D000818:Animals; D053331:Ectodysplasins / Q000235:genetics / Q000378:metabolism*; D053339:Edar Receptor / Q000235:genetics / Q000378:metabolism; D053362:Edar-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D009924:Organ Culture Techniques; D012469:Salivary Glands / Q000196:embryology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D053331:Ectodysplasins; D053339:Edar Receptor; C506009:Edar protein, mouse; D053362:Edar-Associated Death Domain Protein; C506124:Edaradd protein, mouse; D053823:Hedgehog Proteins