During development, mitral cells, the major output neurons of the olfactory
bulb, project their axons caudolaterally into the telencephalon and form t
he lateral olfactory tract (LOT). Two types of guidance cues have been sugg
ested for this projection. First, a long-range factor Slit, which is secret
ed from the septum, repels mitral cell axons into a caudolateral direction.
Second, the pathway of mitral cell axons contains a subset of neurons desi
gnated as lot cells, which guide the axons through short-range interactions
. It is not clear how these two guidance cues relate to each other and how
they share the physiological roles. Here we examined the behavior of mitral
cell axons in organotypic culture on ectopic application of Slit and inhib
ition of endogenous Slit signaling. The results suggested that the short-ra
nge guidance cue in the LOT pathway functions independently from Slit. Furt
hermore, our results showed that removal of the septum and inhibition of Sl
it signaling did not affect the projection of mitral cell axons. Although t
he septum and exogenous Slit can repel olfactory bulb axons, our results ca
st doubts on the physiological relevance of the septum and endogenous Slit
in guiding the projection of mitral cell axons.