RT Journal Article
SR Electronic
T1 Slit1 and Slit2 Proteins Control the Development of the Lateral Olfactory Tract
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5473
OP 5480
DO 10.1523/JNEUROSCI.22-13-05473.2002
VO 22
IS 13
A1 Kim T. Nguyen-Ba-Charvet
A1 Andrew S. Plump
A1 Marc Tessier-Lavigne
A1 Alain Chédotal
YR 2002
UL http://www.jneurosci.org/content/22/13/5473.abstract
AB 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 vivousing mice with targeted deletions in the Slit1 andSlit2 genes. When olfactory bulb explants are cocultured with septum from Slit1- and/orSlit2-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 orSlit2 single-deficient mice but is completely disorganized in Slit1/Slit2double-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 guidancein vivo.