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. J. Comp. Neurol. 482:257–272, 2005. © 2004 Wiley‐Liss, Inc.