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doi: 10.1242/10.1242/dev.00317
Department of Molecular Biology, Umeå University, Umeå, S-901 87, Sweden
* Author for correspondence (e-mail: staffan.bohm{at}molbiol.umu.se)
Accepted 26 November 2002
Olfactory sensory neurons (OSNs) are individually specified to express one
odorant receptor (OR) gene among 
1000 different and project with
precision to topographically defined convergence sites, the glomeruli, in the
olfactory bulb. Although ORs partially determine the location of convergence
sites, the mechanism ensuring that axons with different OR identities do not
co-converge is unknown. RNCAM (OCAM, NCAM2) is assumed to regulate a broad
zonal segregation of projections by virtue of being a homophilic cell adhesion
molecule that is selectively expressed on axons terminating in a defined
olfactory bulb region. We have identified NADPH diaphorase activity as being
an independent marker for RNCAM-negative axons. Analyses of transgenic mice
that ectopically express RNCAM in NADPH diaphorase-positive OSNs show that the
postulated function of RNCAM in mediating zone-specific segregation of axons
is unlikely. Instead, analyses of one OR-specific OSN subpopulation (P2)
reveal that elevated RNCAM levels result in an increased number of P2 axons
that incorrectly co-converge with axons of other OR identities. Both
Gpi-anchored and transmembrane-bound RNCAM isoforms are localized on axons in
the nerve layer, while the transmembrane-bound RNCAM is the predominant
isoform on axon terminals within glomeruli. Overexpressing transmembrane-bound
RNCAM results in co-convergence events close to the correct target glomeruli.
By contrast, overexpression of Gpi-anchored RNCAM results in axons that can
bypass the correct target before co-converging on glomeruli located at a
distance. The phenotype specific for Gpi-anchored RNCAM is suppressed in mice
overexpressing both isoforms, which suggests that two distinct RNCAM
isoform-dependent activities influence segregation of OR-defined axon
subclasses.
Key words: RNCAM, OCAM, NCAM2, apCAM, Fasciclin 2, Neural cell adhesion molecule, Splice variants, Olfactory, Sensory map, Gene expression, Odorant receptors, Axon guidance, Mouse, Glycosylphosphatidylinositol, Fasciculation
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