The emergence of the ectodysplasin pathway.

The genes coding for the proteins of the ectodermal dysplasin pathway, EDA, EDAR and EDA2R are found in genomes of animals that long predate vertebrates. We show that EDA, EDAR and EDA2R are expressed in the sea anemone. A fourth gene in the pathway, EDARADD, only appears with the cyclostomes. With the appearance of EDARADD, the ectodermal dysplasin system was now complete, and the skin appendages emerged, first in the form of the cyclostome's 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.