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The Journal of Neuroscience, August 2, 2006, 26(31):8082-8091; doi:10.1523/JNEUROSCI.1342-06.2006

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Development/Plasticity/Repair
Slit Proteins Regulate Distinct Aspects of Retinal Ganglion Cell Axon Guidance within Dorsal and Ventral Retina

Hannah Thompson, ^* Olivier Camand, ^* David Barker, and Lynda Erskine

Divisions of Visual Science and Molecular Genetics, Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom

Correspondence should be addressed to Dr. Lynda Erskine, Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK. Email: l.erskine{at}ucl.ac.uk

An early step in the formation of the optic pathway is the directed extension of retinal ganglion cell (RGC) axons into the optic fiber layer (OFL) of the retina in which they project toward the optic disc. Using analysis of knock-out mice and in vitro assays, we found that, in the mammalian retina, Slit1 and Slit2, known chemorepellents for RGC axons, regulate distinct aspects of intraretinal pathfinding in different regions of the retina. In ventral and, to a much lesser extent, dorsal retina, Slits help restrict RGC axons to the OFL. Additionally, within dorsal retina exclusively, Slit2 also regulates the initial polarity of outgrowth from recently differentiated RGCs located in the retinal periphery. This regional specificity occurs despite the fact that Slits are expressed throughout the retina, and both dorsal and ventral RGCs are responsive to Slits. The gross morphology and layering of the retina of the slit-deficient retinas is normal, demonstrating that these distinct guidance defects are not the result of changes in the organization of the tissue. Although displaced or disorganized, the aberrant axons within both dorsal and ventral retina exit the eye. We also have found that the lens, which because of its peripheral location within the developing eye is ideally located to influence the initial direction of RGC axon outgrowth, secretes Slit2, suggesting this is the source of Slit regulating OFL development. These data demonstrate clearly that multiple mechanisms exist in the retina for axon guidance of which Slits are an important component.

Key words: Robo; Slit; growth cone; axon guidance; visual system; retinal ganglion cell

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Received March 30, 2006; revised June 19, 2006; accepted June 26, 2006.

Correspondence should be addressed to Dr. Lynda Erskine, Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK. Email: l.erskine{at}ucl.ac.uk

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				F. Causeret Differential Role of Slits in Dorsal versus Ventral Retinal Axon Guidance J. Neurosci., September 27, 2006; 26(39): 9839 - 9840. [Full Text] [PDF]

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