Short-Range Guidance of Olfactory Bulb Axons Is Independent of Repulsive Factor Slit

Abstract

During development, mitral cells, the major output neurons of the olfactory bulb, project their axons caudolaterally into the telencephalon and form the lateral olfactory tract (LOT). Two types of guidance cues have been suggested for this projection. First, a long-range factor Slit, which is secreted from the septum, repels mitral cell axons into a caudolateral direction. Second, the pathway of mitral cell axons contains a subset of neurons designated 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 inhibition of endogenous Slit signaling. The results suggested that the short-range guidance cue in the LOT pathway functions independently from Slit. Furthermore, our results showed that removal of the septum and inhibition of Slit signaling did not affect the projection of mitral cell axons. Although the septum and exogenous Slit can repel olfactory bulb axons, our results cast doubts on the physiological relevance of the septum and endogenous Slit in guiding the projection of mitral cell axons.

Robo1 and Robo2 Control the Development of the Lateral Olfactory Tract

“…Thus, the removal of the septum or the addition of a Robo1 ectodomain in whole-telencephalon organotypic cultures did not affect the projection of mitral cell axons (Hirata et al, 2001). Our results demonstrate that the distribution of lot1-expressing cells is not significantly perturbed in Slit1-, Slit2-, Slit1;Slit2-, or Robo1-, Robo2-and Robo1;Robo2-deficient mice.…”

“…It has been shown previously that LOT axons may be guided through short-range interaction with so-called "lot cells," which may act as guidepost cells (Hirata et al, 2001). Lot cells can be visualized with the monoclonal antibody mAb lot1 and migrate ventrally from the dorsal telencephalic vesicle to their final position (Sato et al, 1998;Tomioka et al, 2000).…”

The olfactory bulb as an independent developmental domain

“…16 Such cells have been identi®ed by the mAb lot1 as a subset of early-generated neurons formed exclusively in the neocortex, which migrate to reach their position in the basal telencephalon, thereby enclosing the LOT area. 68,69 These lot1-positive cells may produce factors that either attract or support axonal outgrowth. Indeed, lot1-positive cells seem to form a border in most areas of the olfactory cortex, beyond which LOT axons do not grow.…”

“…72,73 However, Slit-2 may not play a simple role in this process. 36,69 Recently, the group of Pini suggested that a concurrent cue may also exist that is responsible for the repellent activity of the septum and that which may be different from Slit-2 (see Figure 2). 74 LOT axons also respond selectively to the secreted semaphorins.…”

“…One example is that of Slit-2, a well-known chemorepellent for axonal guidance that seems to be a positive regulator of sensory axonal branching. 69,82 On the other hand, other studies suggest that different cues may The olfactory bulb L Lo  pez-Mascaraque and F de Castro be used to induce collateral axon branching than for axonal pathfinding. 81 The lot1-positive cells, which do not seem to be involved in the collateral branching of the OB mitral cells could provide an example of this phenomenon.…”