Requirement for Slit-1 and Robo-2 in Zonal Segregation of Olfactory Sensory Neuron Axons in the Main Olfactory Bulb

Cho, Jin Hyung; Lépine, Manon; Andrews, William; Parnavelas, John G.; Cloutier, Jean-François

doi:10.1523/jneurosci.2217-07.2007

Cited by 111 publications

(133 citation statements)

References 52 publications

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“…Probes were synthesized from cDNA clones encoding Kirrel1, Kirrel2 and Kirrel3 (kind gifts of Dr David Ginty, Johns Hopkins School of Medicine, Baltimore, USA), and G αo and G αi2 (Cloutier et al, 2002). Fresh frozen brains or nasal cavities were cryosectioned at 20 μm, fixed, and processed as previously described (Cho et al, 2007).…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Kirrel3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression

et al. 2013

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SUMMARYThe accessory olfactory system controls social and sexual interactions in mice that are crucial for survival. Vomeronasal sensory neurons (VSNs) form synapses with dendrites of second order neurons in glomeruli of the accessory olfactory bulb (AOB). Axons of VSNs expressing the same vomeronasal receptor coalesce into multiple glomeruli within spatially conserved regions of the AOB. Here we examine the role of the Kirrel family of transmembrane proteins in the coalescence of VSN axons within the AOB. We find that Kirrel2 and Kirrel3 are differentially expressed in subpopulations of VSNs and that their expression is regulated by activity. Although Kirrel3 expression is not required for early axonal guidance events, such as fasciculation of the vomeronasal tract and segregation of apical and basal VSN axons in the AOB, it is necessary for proper coalescence of axons into glomeruli. Ablation of Kirrel3 expression results in disorganization of the glomerular layer of the posterior AOB and formation of fewer, larger glomeruli. Furthermore, Kirrel3 −/− mice display a loss of male-male aggression in a resident-intruder assay. Taken together, our results indicate that differential expression of Kirrels on vomeronasal axons generates a molecular code that dictates their proper coalescence into glomeruli within the AOB.

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Section: In Situ Hybridizationmentioning

confidence: 99%

Kirrel3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression

et al. 2013

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“…Neuropilin-2 (Nrp2) and Robo-2 are good candidate guidance molecules determining the D -V axis, because they show graded expression in the OE (Norlin et al 2001;Cho et al 2007). Nrp2 is expressed in a ventral-high and dorsallow gradient, whereas Robo-2 expression shows a dorsal-high and ventral-low gradient in the OE and OSN axon termini (Fig.…”

Section: Mechanisms Of Olfactory Map Formation In Mammals Topographicmentioning

confidence: 99%

“…1B). Mice deficient for Robo-2 have defective axonal projections along the D-V axis (Cho et al 2007;Nguyen-Ba-Charvet et al 2008).…”

Section: Mechanisms Of Olfactory Map Formation In Mammals Topographicmentioning

confidence: 99%

Topographic Mapping--The Olfactory System

Imai¹,

Sakano²,

Vosshall³

2010

Cold Spring Harbor Perspectives in Biology

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Sensory systems must map accurate representations of the external world in the brain. Although the physical senses of touch and vision build topographic representations of the spatial coordinates of the body and the field of view, the chemical sense of olfaction maps discontinuous features of chemical space, comprising an extremely large number of possible odor stimuli. In both mammals and insects, olfactory circuits are wired according to the convergence of axons from sensory neurons expressing the same odorant receptor. Synapses are organized into distinctive spherical neuropils-the olfactory glomeruli-that connect sensory input with output neurons and local modulatory interneurons. Although there is a strong conservation of form in the olfactory maps of mammals and insects, they arise using divergent mechanisms. Olfactory glomeruli provide a unique solution to the problem of mapping discontinuous chemical space onto the brain.T he olfactory system detects airborne organic and inorganic chemicals that originate from plant and animal metabolites and environmental and industrial sources. Odors mediate both innate and learned behaviors such as attraction and aversion, governing decisions to eat, mate, attack or flee from aggressors and predators. A remarkable feature of the olfactory system is the extraordinary diversity of possible odor molecules that exist. Although accurate measurements can be made of the detection range of visual wavelengths or auditory frequencies in humans, there are no reliable estimates of the number of odorous molecules that exist on earth or those that can be detected by a given animal species (Gilbert 2008). Nevertheless, the number of possible odorants is thought to be high, in the range of many thousands. Beyond odor detection lies the problem of odor discrimination: how can chemicals with slightly different physical properties be discriminated and associated with distinct odor percepts?Experiments investigating the molecular logic of olfaction over the last 20 years have led to major insights into how animals solve the problem of detecting and discriminating a vast number of different odor stimuli (Axel 1995). Four organizational principles have emerged from this work. First, large numbers of distinct odorant receptor (OR) genes are dedicated

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“…Slit was first identified in Drosophila as a molecule secreted by midline cells, and was later shown to repel the extension of axons expressing Robo receptors (Brose et al, 1999;Kidd et al, 1999;Seeger et al, 1993) and to regulate the migration of cells such as neuronal precursors . In the olfactory system, members of the Slit and Robo families are expressed in a specific spatiotemporal pattern and play important roles in the guidance of olfactory sensory axons (Cho et al, 2007;Marillat et al, 2002;Nguyen-Ba-Charvet et al, 2008;Yuan et al, 1999). Whether OECs, which have the same developmental origin as olfactory sensory neurons, are also responsive to Slits is unknown.…”

Section: Introductionmentioning

confidence: 99%

Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition

Huang

Wang

et al. 2011

Journal of Cell Science

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SummaryOlfactory ensheathing cells (OECs) migrate from the olfactory epithelium towards the olfactory bulb during development. However, the guidance mechanism for OEC migration remains a mystery. Here we show that migrating OECs expressed the receptor of the repulsive guidance factor Slit-2. A gradient of Slit-2 in front of cultured OECs first caused the collapse of the leading front, then the reversal of cell migration. These Slit-2 effects depended on the Ca 2+ release from internal stores through inositol (1,4,5)-triphosphate receptor channels. Interestingly, in response to Slit-2 stimulation, collapse of the leading front required the activation of the F-actin severing protein cofilin in a Ca 2+ -dependent manner, whereas the subsequent reversal of the soma migration depended on the reversal of RhoA activity across the cell. Finally, the Slit-2-induced repulsion of cell migration was fully mimicked by co-application of inhibitors of F-actin polymerization and RhoA kinase. Our findings revealed Slit-2 as a repulsive guidance factor for OEC migration and an unexpected link between Ca 2+ and cofilin signaling during Slit-2-triggered repulsion.

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Requirement for Slit-1 and Robo-2 in Zonal Segregation of Olfactory Sensory Neuron Axons in the Main Olfactory Bulb

Cited by 111 publications

References 52 publications

Kirrel3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression

Kirrel3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression

Topographic Mapping--The Olfactory System

Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition

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