BIG-2 Mediates Olfactory Axon Convergence to Target Glomeruli

Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
Neuron (Impact Factor: 15.05). 04/2008; 57(6):834-46. DOI: 10.1016/j.neuron.2008.01.023
Source: PubMed


Olfactory sensory neurons expressing a given odorant receptor converge axons onto a few topographically fixed glomeruli in the olfactory bulb, leading to establishment of the odor map. Here, we report that BIG-2/contactin-4, an axonal glycoprotein belonging to the immunoglobulin superfamily, is expressed in a subpopulation of mouse olfactory sensory neurons. A mosaic pattern of glomerular arrangement is observed with strongly BIG-2-positive, weakly positive, and negative axon terminals in the olfactory bulb, which is overlapping but not identical with those of Kirrel2 and ephrin-A5. There is a close correlation between the BIG-2 expression level and the odorant receptor choice in individual sensory neurons. In BIG-2-deficient mice, olfactory sensory neurons expressing a given odorant receptor frequently innervate multiple glomeruli at ectopic locations. These results suggest that BIG-2 is one of the axon guidance molecules crucial for the formation and maintenance of functional odor map in the olfactory bulb.

  • Source
    • "In the mouse, the first olfactory sensory axons enter the bulb at ∼E15, while glomeruli are only detectable postnatally (Doucette, 1989; Royal and Key, 1999; Conzelmann et al., 2001; Potter et al., 2001). Targeting of sensory axons from the OE to the bulb has been studied extensively in mice (Wang et al., 1998; Schwarting et al., 2000; Vassalli et al., 2002; Cutforth et al., 2003; Imai et al., 2006, 2009; Serizawa et al., 2006; Cho et al., 2007; Col et al., 2007; Kaneko-Goto et al., 2008; Nguyen-Ba-Charvet et al., 2008; Takeuchi et al., 2010). With few exceptions, most of this work has concentrated on glomerular formation near the time of birth or thereafter. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Olfactory sensory axons target well-defined intermediate targets in the zebrafish olfactory bulb called protoglomeruli well before they form odorant receptor-specific glomeruli. A subset of olfactory sensory neurons are labeled by expression of the or111-7:IRES: GAL4 transgene whose axons terminate in the central zone (CZ) protoglomerulus. Previous work has shown that some of these axons misproject to the more dorsal and anterior dorsal zone (DZ) protoglomerulus in the absence of Netrin 1/Dcc signaling. In search of additional cues that guide these axons to the CZ, we found that Semaphorin 3D (Sema3D) is expressed in the anterior bulb and acts as a repellent that pushes them towards the CZ. Further analysis indicates that Sema3D signaling is mediated through Nrp1a, while Nrp2b also promotes CZ targeting but in a Sema3D-independent manner. nrp1a, nrp2b and dcc transcripts are detected in or111-7 transgene-expressing neurons early in development and both Nrp1a and Dcc act cell-autonomously in sensory neurons to promote accurate targeting to the CZ. dcc and nrp1a double mutants have significantly more DZ misprojections than either single mutant, suggesting that the two signaling systems act independently and in parallel to direct a specific subset of sensory axons to their initial protoglomerular target.
    Preview · Article · Jan 2016 · Development
  • Source
    • "Contactin-4 Is Expressed by RGCs that Target AOS Nuclei To explore the molecular signals controlling development of parallel eye-to-brain circuits, we screened the expression patterns of IgG superfamily proteins in retinorecipient targets and identified Contactin-4 (CNTN4) as a candidate. CNTN4 belongs to a small family of axon-associated cell adhesion molecules within the IgG superfamily that has six Ig domains and four fibronectin type III domains and is glycophosphatidylinositol (GPI)-anchored to the plasma membrane (Yoshihara et al., 1995; Kaneko-Goto et al., 2008; reviewed in Shimoda and Watanabe, 2009). Labeling of retinorecipient targets by intravitreal injections of cholera toxin beta (CTb-594) followed by staining of tissue sections with an antibody specific for CNTN4 (Kaneko-Goto et al., 2008; Figures S1E and S1H) revealed that it was selectively expressed in AOS targets: it was present at high levels in the developing NOT (Figures 1D–1F) and at lower levels in the MTNd and MTNv (Figures 1G–1I). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The mammalian eye-to-brain pathway includes more than 20 parallel circuits, each consisting of precise long-range connections between specific sets of retinal ganglion cells (RGCs) and target structures in the brain. The mechanisms that drive assembly of these parallel connections and the functional implications of their specificity remain unresolved. Here we show that in the absence of contactin 4 (CNTN4) or one of its binding partners, amyloid precursor protein (APP), a subset of direction-selective RGCs fail to target the nucleus of the optic tract (NOT)-the accessory optic system (AOS) target controlling horizontal image stabilization. Conversely, ectopic expression of CNTN4 biases RGCs to arborize in the NOT, and that process also requires APP. Our data reveal critical and novel roles for CNTN4/APP in promoting target-specific axon arborization, and they highlight the importance of this process for functional development of a behaviorally relevant parallel visual pathway. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · May 2015 · Neuron
  • Source
    • "Eml5, which belongs to a family of proteins that regulate microtubule dynamics, is found in axons in several regions of the brain. These data are consistent with several other known activity-dependent mRNAs that encode axonal or synaptic proteins (Imai et al. 2006;Kaneko-Goto et al. 2008;Imai et al. 2009). Another commonality among the activity-dependent OSN mRNAs is the ability of several of their encoded proteins to bind calcium directly or to interact with calcium-binding proteins. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Activity-dependent survival of olfactory sensory neurons (OSNs) may allow animals to tune their olfactory systems to match their odor environment. Activity-dependent genes should play important roles in this process, motivating experiments to identify them. Both unilateral naris occlusion of mice for 6 days and genetic silencing of OSNs decreased S100A5, Lrrc3b, Kirrel2, Slc17a6, Rasgrp4, Pcp4l1, Plcxd3, and Kcnn2 while increasing Kirrel3. Naris occlusion also decreased Eml5, Ptprn, and Nphs1. OSN number was unchanged and stress-response mRNAs were unaffected after 6 days of naris occlusion. This leaves odor stimulation as the most likely cause of differential abundance of these mRNAs, but through a mechanism that is slow or indirect for most because 30–40min of odor stimulation increased only 3 of 11 mRNAs decreased by naris occlusion: S100A5, Lrrc3b, and Kirrel2. Odorant receptor (OR) mRNAs were significantly more variable than the average mRNA, consistent with difficulty in reliably detecting changes in these mRNAs after 6 days of naris occlusion. One OR mRNA, Olfr855, was consistently decreased, however. These results suggest that the latency from the cessation of odor stimulation to effects on activity-dependent OSN survival must be a week or more in juvenile mice.
    Full-text · Article · Apr 2014 · Chemical Senses
Show more