Cloning and expressions of three mammalian homologues of Drosophila slit suggest possible roles for Slit in the formation and maintenance of the nervous system.

In Drosophila embryogenesis, the slit gene has been shown to play a critical role in CNS midline formation. However, no slit homologues have been reported in vertebrates. Here, we have identified mammalian homologues of the slit gene (human Slit-1, Slit-2, Slit-3, and rat Slit-1). Each Slit gene encodes a putative secreted protein, which contains conserved protein-protein interaction domains including leucine-rich repeats (LRR) and epidermal growth factor (EGF)-like motifs, like that of the Drosophila protein. Northern blot analysis revealed that the human Slit-1, -2, and -3 mRNAs are exclusively expressed in the brain, spinal cord, and thyroid, respectively. In situ hybridization studies indicated that the rat Slit-1 mRNA is specifically expressed in the neurons of fetal and adult forebrains. Our data suggest that Slit genes form an evolutionary conserved group in vertebrates and invertebrates, and that the mammalian Slit proteins may participate in the formation and maintenance of the nervous and endocrine systems by protein-protein interactions.