Reggies are plasma membrane-associated proteins and characteristic markers of lipid-raft microdomains. They are highly conserved from flies to humans and have been implicated in axon regeneration and cell process and contact formation, possibly providing functional platforms for cell-signaling in neurons and other cell types. We analyzed reggie mRNA and protein expression patterns during early zebrafish development. All three zebrafish genes, re-1a, -2a, and -2b, span a considerably diverse set of expression patterns, and their proteins are induced maternally, showing ubiquitous expression at early stages. Although re-2a mRNA can be observed in differentiating neurons in the brain, spinal cord, and neurogenic placodes, re-2b is transcribed mainly in head mesoderm, in neural crest derivates, and along somite boundaries, re-1a mRNA is present at high levels in expression domains that overlap with the combined expression pattern of both re-2 genes except at the somites, where it complements the pattern of re-2b. Immunostaining on embryos reveals reggie protein localization at the cell membrane, at cell-cell contacts, and along all early axon tracts. The early phase of reggie expression suggests a basic and ubiquitous function during the first stages of embryogenesis and into the gastrula period. Upon segmentation, a second phase of expression shows distinctly localized expression patterns, indicating tissue-specific roles and an involvement of re-1a/re-2a in neural development. © 2004 Wiley-Liss, Inc.