Abstract
Olfactory sensory neuron (OSN) axons coalesce into specific glomeruli in the olfactory bulb (OB) according to their odorant receptor (OR) expression. Several guidance molecules enhance the coalescence of homotypic OSN projections, in an OR-specific- and neural-activity-dependent manner. However, the mechanism by which homotypic OSN axons are organized into glomeruli is unsolved. We previously reported that the clustered protocadherin-α (Pcdh-α) family of diverse cadherin-related molecules plays roles in the coalescence and elimination of homotypic OSN axons throughout development. Here we showed that the elimination of small ectopic homotypic glomeruli required the constitutive expression of a Pcdh-α isoform and Pcdh-α's cytoplasmic region, but not OR specificity or neural activity. These results suggest that Pcdh-α proteins provide a cytoplasmic signal to regulate repulsive activity for homotypic OSN axons independently of OR expression and neural activity. The counterbalancing effect of Pcdh-α proteins for the axonal coalescence mechanisms mediated by other olfactory guidance molecules indicate a possible mechanism for the organization of homotypic OSN axons into glomeruli during development.
Highlights
The olfactory system can recognize and discriminate an enormous number of odor molecules in the external environment
We propose that Pcdh-α has an activity that causes repulsion in homotypic Olfactory sensory neuron (OSN) axons, that is different from the coalescence activity provided by other olfactory guidance molecules
To confirm whether Pcdh-α is involved in the axonal coalescence of homotypic OSNs in the glomeruli in ventral and dorsal positions of the olfactory bulb (OB), we examined the axonal coalescence of OSNs expressing the odorant receptor (OR) MOR28 and mOR-EG
Summary
The olfactory system can recognize and discriminate an enormous number of odor molecules in the external environment. The coalescence of OSN axons into glomeruli is directed by the expressed OR and is dependent on neural activity (Feinstein and Mombaerts, 2004; Feinstein et al, 2004; Mombaerts, 2006; Serizawa et al, 2006) In this process, guidance molecules including cell adhesion molecules and receptors organize the OSN axon projections; these guidance molecules include ephrin/Eph, Semaphorin/neuropilin, Plexin, BIG-2, and Kirrel2/3 (Schwarting et al, 2000, 2004; Walz et al, 2002; Cutforth et al, 2003; Taniguchi et al, 2003; Imai et al, 2006; Serizawa et al, 2006; Col et al, 2007; Kaneko-Goto et al, 2008; Takeuchi et al, 2010). The distinct expression levels and combinations of guidance molecules in the OSNs constitute one basic mechanism for the approximate projection and coalescence of OSN axons
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