Distinct but overlapping expression patterns of two vertebrate slit homologs implies functional roles in CNS development and organogenesis

Abstract

The Drosophila slit gene (sli) encodes a secreted leucine-rich repeat-containing protein (slit) expressed by the midline glial cells and required for normal neural development. A putative human sli homolog, SLIT1, has previously been identified by EST database scanning. We have isolated a second human sli homolog, SLIT2, and its murine homolog Slit2. Both SLIT1 and SLIT2 proteins show approximately 40% amino acid identity to slit and 60% identity to each other. In mice, both genes are expressed during CNS development in the floor plate, roof plate and developing motor neurons. As floor plate represents the vertebrate equivalent to the midline glial cells, we predict a conservation of function for these vertebrate homologs. Each gene shows additional but distinct sites of expression outside the CNS suggesting a variety of functions for these proteins.

Cloning and expression of three zebrafish roundabout homologs suggest roles in axon guidance and cell migration

“…In vertebrates, Slits have been shown to repel several types of extending axons as well as migrating neurons Hu, 1999;Li et al, 1999;Nguyen Ba-Charvet et al, 1999;Niclou et al, 2000;Wu et al, 1999;Zhu et al, 1999). The complementary expression of Slits and Robos during vertebrate development Holmes et al, 1998; and the binding of Slit and Robo in cellular assays Li et al, 1999;Chen et al, 2000) suggest that the Robo-Slit receptor-ligand relationship is conserved in vertebrates, but the functions of vertebrate Robos are largely unproven, especially in vivo.…”

“…While the expression patterns of slit1, 2, and 3 have been examined in detail (e.g., Itoh et al, 1998;Holmes et al, 1998;Li et al, 1999;, the expression studies of vertebrate robos are much less complete. The expression patterns of mammalian robo1 and 2 have been studied in the developing spinal cord Wang et al, 1999;, eye (Erskine et al, 2000;Niclou et al, 2000;Ringstedt et al, 2000), kidney (Piper et al, 2000), olfactory bulb, and hippocampus (Nguyen Ba-Charvet et al, 1999).…”

“…Recently, Slit has been shown to be the chemorepulsive midline signal for the Robo receptor in Drosophila . In vertebrates, three Slit homologs have been cloned in mammals Holmes et al, 1998;Itoh et al, 1998;Li et al, 1999), while only one Xenopus Slit , one partial chick Slit , and two zebrafish Slits (Yeo et al, 2001) have so far been described. Vertebrate Slits have been shown in vitro to act as repellents for several classes of axons (e.g., Brose et al, 1999;Chen et al, 2000;Li et al, 1999;Nguyen Ba-Charvet et al, 1999;Niclou et al, 2000).…”

Robo family of proteins exhibit differential expression in mouse spinal cord and Robo-Slit interaction is required for midline crossing in vertebrate spinal cord

“…Three vertebrate Slit proteins have been identified as the ligands of Robo receptors and shown to act as repellent molecules (Holmes et al, 1998;Itoh et al, 1998;Brose et al, 1999;Li et al, 1999;Yuan et al, 1999b). The vertebrate Slit proteins have been shown to bind Robo1 and Robo2 proteins in cell binding and immunoprecipitation assays (Brose et al, 1999;Li et al, 1999).…”

Short-Range Guidance of Olfactory Bulb Axons Is Independent of Repulsive Factor Slit

“…Previous studies have identified three members of the mouse Slit family (Holmes et al, 1998;Itoh et al, 1998;Nakayama et al, 1998). Among these, Slit1 and Slit2 are expressed in the septum at E12.5 Tuyen et al, 1999) (Fig.…”