Robo-2 Controls the Segregation of a Portion of Basal Vomeronasal Sensory Neuron Axons to the Posterior Region of the Accessory Olfactory Bulb

Abstract

The ability of sensory systems to detect and process information from the environment relies on the elaboration of precise connections between sensory neurons in the periphery and second order neurons in the CNS. In mice, the accessory olfactory system is thought to regulate a wide variety of social and sexual behaviors. The expression of the Slit receptors Robo-1 and Robo-2 in vomeronasal sensory neurons (VSNs) suggests they may direct the stereotypic targeting of their axons to the accessory olfactory bulb (AOB). Here, we have examined the roles of Robo-1 and Robo-2 in the formation of connections by VSN axons within the AOB. While Robo-1 is not necessary for the segregation of VSN axons within the anterior and posterior regions of the AOB, Robo-2 is required for the targeting of some basal VSN axons to the posterior region of the AOB but is dispensable for the fasciculation of VSN axons. Furthermore, the specific ablation of Robo-2 expression in VSNs leads to mistargeting of a portion of basal VSN axons to the anterior region of the AOB, indicating that Robo-2 expression is required on projecting VSN axons. Together, these results identify Robo-2 as a receptor that controls the targeting of basal VSN axons to the posterior AOB.

Moving away from the midline: new developments for Slit and Robo

“…Slits have been shown to bind with similar affinity to all of the Robo receptors using evolutionarily conserved binding residues (Brose et al, 1999;Morlot et al, 2007). However, in different systems, Slits mediate differing effects; for instance OSN axonal targeting is modulated by Slit1 and Slit2, but not by Slit3 (Prince et al, 2009). It will therefore be important to identify the molecules, such as coreceptors, that mediate such ligand specificity.…”

“…3B). Basal VSN axons are also misrouted in Slit1/Slit2 double-heterozygous mice, but not in Slit3 knockouts, thus establishing a role for Slit2, in addition to Slit1, in the proper targeting of VSN axons to the AOB (Prince et al, 2009). Although VSNs express both Robo1 and Robo2 receptors, only Robo2 appears to be essential for maintaining proper segregation of VSN axons in the AOB.…”

“…A role for Slits and Robos in axonal targeting has best been described in the mouse olfactory system (Cho et al, 2009). Briefly, in the principal olfactory system, olfactory sensory neurons (OSNs) extend from the olfactory epithelium to the olfactory bulb (OB) where they connect with the major OB output neurons, mitral cells and tufted cells.…”

“…Although VSNs express both Robo1 and Robo2 receptors, only Robo2 appears to be essential for maintaining proper segregation of VSN axons in the AOB. Indeed, when Robo2 is specifically deleted from VSNs, some of the basal VSN neurons are misrouted into the anterior AOB, indicating that Slit1 function is primarily mediated by Robo2 (Prince et al, 2009). …”

Molecular Switches in the Development and Fate Specification of Vomeronasal Neurons: Figure 1.

“…Previous evidence has suggested a role of axon guidance molecules in the segregation of vomeronasal axons into their final position in the AOB (Knöll et al, 2001(Knöll et al, , 2003Walz et al, 2002;Prince et al, 2009), but until recently, no study had proposed molecular candidates for the regulation of maturation and fate choice of newly generated vomeronasal neurons. In a recent article published in The Journal of Neuroscience, however, Enomoto et al (2011) showed that Bcl11b/Ctip2, a zinc finger transcription factor involved in regulating corticofugal fate of deep-layered neocortical neurons , is crucial for maturation and fate determination of vomeronasal neurons, for establishing axonal projections to the AOB, and for correct layering of intrinsic AOB neurons.…”