Mouse studies have highlighted the requirement of the extracellular matrix Fras and Frem proteins for embryonic epidermal adhesion. Mutations of the genes encoding some of these proteins underlie the blebs mouse mutants, whereas mutations in human FRAS1 and FREM2 cause Fraser syndrome, a congenital disorder characterized by embryonic blistering and renal defects. We have cloned the zebrafish homologues of these genes and characterized their evolutionary diversification and expression during development. The fish gene complement includes fras1, frem1a, frem1b, frem2a, frem2b, and frem3, which display complex overlapping and complementary expression patterns in developing tissues including the pharyngeal arches, hypochord, musculature, and otic vesicle. Expression during fin development delineates distinct populations of epidermal cells which have previously only been described at a morphological level. We detect relatively little gene expression in epidermis or pronephros, suggesting that the essential role of these proteins in mediating their development in humans and mice is recently evolved. Developmental Dynamics 237:3295–3304, 2008. © 2008 Wiley-Liss, Inc.