Retinal ganglion cell axon guidance in the mouse optic chiasm: expression and function of robos and slits.
The ventral midline of the nervous system is an important choice point at which growing axons decide whether to cross and project contralaterally or remain on the same side of the brain. In Drosophila, the decision to cross or avoid the CNS midline is controlled, at least in part, by the Roundabout (Robo) receptor on the axons and its ligand, Slit, an inhibitory extracellular matrix molecule secreted by the midline glia. Vertebrate homologs of these molecules have been cloned and have also been implicated in regulating axon guidance. Using in situ hybridization, we have determined the expression patterns of robo1,2 and slit1,2,3 in the mouse retina and in the region of the developing optic chiasm, a ventral midline structure in which retinal ganglion cell (RGC) axons diverge to either side of the brain. The receptors and ligands are expressed at the appropriate time and place, in both the retina and the ventral diencephalon, to be able to influence RGC axon guidance. In vitro, slit2 is inhibitory to RGC axons, with outgrowth of both ipsilaterally and contralaterally projecting axons being strongly affected. Overall, these results indicate that Robos and Slits alone do not directly control RGC axon divergence at the optic chiasm and may additionally function as a general inhibitory guidance system involved in determining the relative position of the optic chiasm at the ventral midline of the developing hypothalamus.
Erskine
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Department of Pathology, Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA. le63@columbia.edu
Williams
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Brose
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Kidd
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Rachel
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Goodman
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Tessier-Lavigne
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Mason
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D000818:Animals; D001369:Axons / Q000502:physiology*; D004027:Diencephalon / Q000196:embryology*; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009897:Optic Chiasm / Q000196:embryology*; D009924:Organ Culture Techniques; D011971:Receptors, Immunologic / Q000235:genetics*; D012160:Retina / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C120010:Slit1 protein, mouse