title: The ectodysplasin pathway in feather tract development.
abstract: The ectodysplasin pathway, comprising the ligand ectodysplasin, its receptor Edar and a dedicated death domain adaptor protein Edaradd, plays an important role in epidermal organ formation in mammals. Mutations in the genes encoding these proteins cause dysplasia or absence of teeth, sweat glands and hair follicles. However, the relative position of this pathway in the regulatory hierarchy directing follicle formation remains unclear. In this work, the chicken orthologs of Eda, Edar and Edaradd were cloned to exploit the temporal precision of the feather tract system in order to study the role of the ectodysplasin pathway. We find that these genes are expressed in a similar pattern during feather and hair development, with the notable difference that the ligand Eda, which is expressed in the epidermis of the mouse, is expressed in the dermis of the feather tract. Contrary to conclusions reached from the analysis of mutant mice, we find that localization of Edar expression to the nascent placode is coincident or subsequent to the local expression of other markers of placodal differentiation, and not an upstream event in tract patterning. Furthermore, forced expression of BMP and activated beta-catenin demonstrate that local expression of Edar is dictated by the interaction between these two pathways. These results suggest that activation of the ectodysplasin pathway may be permissive for activating signals to overcome signals that inhibit placode formation, but the function of this pathway in the specification of follicle initiation lies downstream of other patterning events.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Houghton
authors.forename: Catherine
authors.initials: C
authors.lastname: Lindon
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Morgan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation; D002642:Chick Embryo; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D053331:Ectodysplasins; D053339:Edar Receptor; D004817:Epidermis / Q000378:metabolism*; D005241:Feathers / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D053338:Receptors, Ectodysplasin; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; D053331:Ectodysplasins; C506019:Eda protein, mouse; D053339:Edar Receptor; C506009:Edar protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D053338:Receptors, Ectodysplasin; D018124:Receptors, Tumor Necrosis Factor