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We show that\n                    <jats:italic>EDA, EDAR<\/jats:italic>\n                    and\n                    <jats:italic>EDA2R<\/jats:italic>\n                    are expressed in the sea anemone. A fourth gene in the pathway,\n                    <jats:italic>EDARADD<\/jats:italic>\n                    , only appears with the cyclostomes. With the appearance of\n                    <jats:italic>EDARADD,<\/jats:italic>\n                    the ectodermal dysplasin system was now complete, and the skin appendages emerged, first in the form of the cyclostome\u2019s keratinized proto-teeth, until finally, feathers and then mammalian hair and eccrine glands evolved. We elaborate on the specific roles of the ectodermal dysplasin pathway proteins: EDA releases its extracellular circulating component, switching on the pathway at the appropriate stage in embryological development. EDA binds to EDAR, whose location in the embryo has been specified by a reaction-diffusion system. The EDA\/EDAR complex now binds to intracellular EDARADD, directing the expression of downstream proteins that orchestrate the mechanics of the cell movements, building the placodes and the appropriate skin appendages.\n                  <\/jats:p>","DOI":"10.1515\/biol-2025-1345","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:56:08Z","timestamp":1784033768000},"source":"Crossref","is-referenced-by-count":0,"title":["The emergence of the ectodysplasin pathway"],"prefix":"10.1515","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3557-6854","authenticated-orcid":false,"given":"Wilfred Donald","family":"Stein","sequence":"first","affiliation":[{"name":"Silberman Institute of Life Sciences , Hebrew University , Jerusalem , 91904 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6068-901X","authenticated-orcid":false,"given":"Thomas","family":"Litman","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology , University of Copenhagen , 2200 , Copenhagen N , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"2026102813560773758_j_biol-2025-1345_ref_001","doi-asserted-by":"crossref","unstructured":"Biggs, LC, Mikkola, ML. 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