XB51 protein is known to interact with the amino-terminal of the X11L protein and to be involved in Aβ40 generation, a hallmark of Alzheimer's disease. In this study, we isolated a zebrafish xb51 homologue and analyzed its spatio-temporal expression pattern during early brain development. The xb51 transcript was first detected in the forebrain at 22 hr post-fertilization. Expression of xb51 in the brain persisted by 36 hpf and became more complex in the brain after 48 hpf. The detailed expression domain of xb51 in the dorsal telencephalon was defined by several molecular markers: emx1, dlx2, lim1, islet1, neurod4/zath3, ngn1, her4, and elavl3/huC. The location of xb51-expressing cells was restricted in a subset of cells positive for elavl3/huC and acetylated alpha-tubulin, markers of differentiating and/or differentiated neurons. Together, these results suggest that xb51 may be required for maturation and maintenance of xb51-expressing neurons in the forebrain. Developmental Dynamics 237:3921–3926, 2008. © 2008 Wiley-Liss, Inc.