Nervous and vascular systems grow as parallel networks, indicating common cues in distal targets. We have identified a novel zebrafish gene slit-like 2 (slit12) that might involve in zebrafish central neural and vascular morphogenesis. Whole-mount in situ hybridization of zebrafish embryo detected distinct signals of slit12 transcripts in zebrafish midline structure of central nervous system similar to that of slits. Strong expression is also observed in zebrafish vasculature. Zebrafish slit12 shares amino acid sequence identity of 41% with Homo sapiens slit12 (vasorin) and Mus musculus slit12, and 35%, 33% with Danio rerio slit3, slit2. Analysis of zebrafish slit12 cripto growth factor domain, extracellular matrix protein slit domain, and putative signal peptide confirms that as a secreted and cell-surface protein slit12 may be essential in axon guidance, vessel development, and axis patterning. These results provide evidence that slit12 may play important roles in zebrafish central. nervous system and vascular morphogenesis. (c) 2005 Elsevier Inc. All rights reserved.