The medaka rs-3 locus required for scale development encodes ectodysplasin-A receptor

The bodies of most teleost fish species are covered with specialized subepi thelial structures known as scales. The scale is an epithelial appendage th at differentiates from the dermal mesenchyme. Mammals, on the other hand, h ave no scales, but instead their bodies are covered with hair. Although the ir appearances are quite different, scales and hair can be considered struc turally similar in that both of them are epithelial appendages distributed over the body surface in an orderly pattern. This analogy suggests that the y may have the same evolutionary origin. But, to date, no molecular evidenc e has been presented that links scales and hair. A mutation at the rs-3 loc us of medaka (Oryzias latipes) leads to almost complete loss of scales. We demonstrated that the rs-3 locus encodes ectodysplasin-A receptor (EDAR), w hich is required for the initiation of hair development in mammals. We iden tified a novel transposon inserted in the first intron of EDAR, which cause s aberrant splicing. This work shows that EDAR is required for scale develo pment in fish and suggests that it is an evolutionarily conserved molecule that is required for the development of epithelial appendages in vertebrate s.