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The Journal of Neuroscience, July 1, 2002, 22(13):5473-5480

Slit1 and Slit2 Proteins Control the Development of the Lateral Olfactory Tract

Kim T. Nguyen-Ba-Charvet¹, Andrew S. Plump², Marc Tessier-Lavigne², and Alain Chédotal¹

¹ Institut National de la Santé et de la Recherche Médicale U106, Bâtiment de Pédiatrie, Hôpital de la Salpêtrière, 75013 Paris, France, and ² Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305-5020

The development of olfactory bulb projections that form the lateral olfactory tract (LOT) is still poorly understood. The septum and the olfactory cortex have been shown to secrete diffusible factors repelling olfactory axons in vitro and are likely to cause the axons to avoid the septum region in vivo. Slit2, a member of the Slit gene family, has been proposed to be this septal factor based on its expression in the embryonic septum and its ability to repel and collapse olfactory axons. However, this issue is still controversial, and recent in vitro studies have questioned the role of the septum and Slit proteins in organizing LOT projections. We therefore decided to examine directly the role of Slit proteins in mediating olfactory axon guidance in vivo using mice with targeted deletions in the Slit1 and Slit2 genes. When olfactory bulb explants are cocultured with septum from Slit1- and/or Slit2-deficient mice, the septum repulsive activity for olfactory bulb axons is progressively abolished in a gene dose-dependent manner. Anterograde tracing of olfactory bulb axons showed that the LOT develops normally in Slit1 or Slit2 single-deficient mice but is completely disorganized in Slit1/Slit2 double-deficient embryos, with many axons reaching the midline and entering the septum region. Therefore, our study showed that the septum chemorepellent is a combination of Slit1 and Slit2 and that these molecules play a significant role in olfactory bulb axon guidance in vivo.

Key words: chemorepulsion; olfactory bulb; Slit; Robo; axon guidance; molecular cues

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22135473-08$05.00/0

This article has been cited by other articles:

				K. T. Nguyen-Ba-Charvet, T. Di Meglio, C. Fouquet, and A. Chedotal Robos and Slits Control the Pathfinding and Targeting of Mouse Olfactory Sensory Axons J. Neurosci., April 16, 2008; 28(16): 4244 - 4249. [Abstract] [Full Text] [PDF]

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