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The Journal of Neuroscience, August 22, 2007, 27(34):9094-9104; doi:10.1523/JNEUROSCI.2217-07.2007

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Development/Plasticity/Repair
Requirement for Slit-1 and Robo-2 in Zonal Segregation of Olfactory Sensory Neuron Axons in the Main Olfactory Bulb

Jin Hyung Cho,^1,2 Manon Lépine,^1,2 William Andrews,³ John Parnavelas,³ and Jean-François Cloutier^1,2

¹Montreal Neurological Institute, Centre for Neuronal Survival, Montréal, Québec, Canada H3A 2B4, ²Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada H3A 2B4, and ³Medical Research Council Centre for Developmental Neurobiology, King's College London, London SE1 1UL, United Kingdom

Correspondence should be addressed to Jean-François Cloutier, Montreal Neurological Institute, Centre for Neuronal Survival, 3801 University, Montréal, Québec, Canada H3A 2B4. Email: jf.cloutier{at}mcgill.ca

The formation of precise stereotypic connections in sensory systems is critical for the ability to detect and process signals from the environment. In the olfactory system, olfactory sensory neurons (OSNs) project axons to spatially defined glomeruli within the olfactory bulb (OB). A spatial relationship exists between the location of OSNs within the olfactory epithelium (OE) and their glomerular targets along the dorsoventral axis in the OB. The molecular mechanisms underlying the zonal segregation of OSN axons along the dorsoventral axis of the OB are poorly understood. Using robo-2^–/– (roundabout) and slit-1^–/– mice, we examined the role of the Slit family of axon guidance cues in the targeting of OSN axons during development. We show that a subset of OSN axons that normally project to the dorsal region of the OB mistarget and form glomeruli in the ventral region in robo-2^–/– and slit-1^–/– mice. In addition, we show that the Slit receptor, Robo-2, is expressed in OSNs in a high dorsomedial to low ventrolateral gradient across the OE and that Slit-1 and Slit-3 are expressed in the ventral region of the OB. These results indicate that the dorsal-to-ventral segregation of OSN axons are not solely defined by the location of OSNs within the OE but also relies on axon guidance cues.

Key words: Slit; Robo; axon guidance; olfactory epithelium; olfactory bulb; glomerular targeting

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Received Dec. 16, 2006; revised July 6, 2007; accepted July 9, 2007.

Correspondence should be addressed to Jean-François Cloutier, Montreal Neurological Institute, Centre for Neuronal Survival, 3801 University, Montréal, Québec, Canada H3A 2B4. Email: jf.cloutier{at}mcgill.ca

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