Expression of the vertebrate Slit gene family and their putative receptors, the Robo genes, in the developing murine kidney

The slit (sli) gene, encoding a secreted glycoprotein, has been demonstrate d to play a vital role in axonal guidance in Drosophila melanogaster by act ing as a signalling ligand for the robe receptor (Rothberg, J.M., Jacobs, J .R., Goodman, C.S., Artavanis-Tsakonas, S., 1990. slit: an extracellular pr otein necessary for development of midline glia and commissural axon pathwa ys contains both EGF and LRR domains. Genes Dev. 4, 2169-2187; Kidd, T., Bl and, K.S., Goodman, C.S., 1999. Slit is the midline repellent for the robo receptor in Drosophila. Cell 96, 785-794). Multiple homologs of both sli an d robe have been identified in vertebrates and are thought to play similar roles to their fly counterparts in neural development (Brose, K., Bland, K. S., Wang, K.H., Arnott, D., Henzel, W., Goodman, C.S., Tessier-Lavigne, M., Kidd, T., 1999. Slit proteins bind Robe receptors and have an evolutionari ly conserved role in repulsive axon guidance. Cell 96, 795-806). Slit2 has been shown to bind Robo1, mediating both neuronal and axonal guidance in th e developing central nervous system (CNS), (Brose et al., 1999; Hu, H., 199 9. Chemorepulsion of neuronal migration by Slit2 in the developing mammalia n forebrain. Neuron 23, 703-711). Importantly, both gene families display d istinct expression patterns outside the CNS (Holmes, G.P., Negus, K., Burri dge, L., Raman, S., Algar, E., Yamada, T., Little, M.H., 1998. Distinct but overlapping expression patterns of two vertebrate slit homologs implies fu nctional roles in CNS development and organogenesis. Mech. Dev. 79, 57-72; Yuan, W., Zhou, L., Chen, J.H., Wu, J.Y., Rao, Y., Ornitz, D.M., 1999. The mouse SLIT family: secreted ligands for ROBO expressed in patterns that sug gest a role in morphogenesis and axon guidance. Dev. Biol. 212, 290-306). U sing in situ hybridization on metanephric explant cultures and urogenital t ract sections, the expression patterns of Slit1, 2, 3 and Robo1 and 2 were investigated during murine metanephric development. Slit1 was expressed in the metanephric mesenchyme (MM) surrounding the invading ureteric tree (UT) . Slit2 was expressed at the tips of the UT and both Slit2 and Slid were ex pressed at the far proximal end of the comma shaped and S-shaped bodies. Ex pression of Robo1 was initially diffuse throughout the MM, then upregulated in the pretubular aggregates, and maintained at the distal end of the comm a and S-shaped bodies. Robo2 was detected in the induced MM surrounding the arborizing UT tips and later in the proximal end of the S-shaped bodies. C oincident expression of Robo1 with Slit1 in the metanephric mesenchyme and Robo2, Slit2 and Slid in the far proximal end of the S-shaped bodies was ob served during metanephric development. (C) 2000 Elsevier Science Ireland Lt d. All rights reserved.