Slits contribute to the guidance of retinal ganglion cell axons in the mammalian optic tract.
RGC axons extend in the optic tracts in a manner that correlates with the expression in the hypothalamus and epithalamus of a soluble factor inhibitory to RGC axon outgrowth. Additionally, although the RGC axons extend adjacent to the telencephalon, they do not normally grow into this tissue. Here, we show that slit1 and slit2, known chemorepellents for RGC axons expressed in specific regions of the diencephalon and telencephalon, help regulate optic tract development. In mice lacking slit1 and slit2, a subset of RGC axons extend into the telencephalon and grow along the pial surface but not more deeply into this tissue. Surprisingly, distinct guidance errors occur in the telencephalon of slit1 -/-; slit2 +/- and slit1/2 -/- embryos, suggesting that the precise level of Slits is critical for determining the path followed by individual axons. In mice lacking both slit1 and slit2, a subset of RGC axons also project aberrantly into the epithalamus, pineal and across the dorsal midline. However, many axons reach their primary target, the superior colliculus. This demonstrates that Slits play an important role in directing the guidance of post-crossing RGC axons within the optic tracts but are not required for target innervation.
Thompson
Hannah
H
Divisions of Visual Science and Molecular Genetics, Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Barker
David
D
Camand
Olivier
O
Erskine
Lynda
L
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000502:physiology; D014795:Visual Pathways / Q000196:embryology* / Q000502:physiology; D000098552:Slit Homolog 2 Protein
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C120010:Slit1 protein, mouse; D000098552:Slit Homolog 2 Protein