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Constitutively expressed Protocadherin-α regulates the coalescence and elimination of homotypic olfactory axons through its cytoplasmic region.

Hasegawa S, Hirabayashi T, Kondo T, Inoue K, Esumi S, Okayama A, Hamada S, Yagi T - Front Mol Neurosci (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: KOKORO-Biology Group and CREST-JST, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University Osaka, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Expression of Pcdh-α mRNAs in OSNs of the OE. (A)In situ hybridization histochemistry with an α11 isoform-specific probe and a αCR probe for all the Pcdh-α isoforms at E16.5 (a, b) and P56 (c–f). High magnifications are shown in (e) and (f). Sus, sustentacular cell-body layer; mOSN, mature OSN cell-body layer; iOSN, immature OSN cell-body layer; Basal, basal cell body layer. Scale bars, 100 μm. (B) Single cell RT-PCR analysis of individual OSNs using adult OMP-GFP mice.
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Figure 4: Expression of Pcdh-α mRNAs in OSNs of the OE. (A)In situ hybridization histochemistry with an α11 isoform-specific probe and a αCR probe for all the Pcdh-α isoforms at E16.5 (a, b) and P56 (c–f). High magnifications are shown in (e) and (f). Sus, sustentacular cell-body layer; mOSN, mature OSN cell-body layer; iOSN, immature OSN cell-body layer; Basal, basal cell body layer. Scale bars, 100 μm. (B) Single cell RT-PCR analysis of individual OSNs using adult OMP-GFP mice.

Mentions: Pcdh-α mRNAs are extensively expressed in almost all of the OSNs from E11.5 to adulthood, and Pcdh-α proteins are enriched in the OSN axons and their terminals in the glomeruli (Hasegawa et al., 2008). However, the mechanisms by which the diverse Pcdh-α family contributes to the axonal coalescence into glomeruli remain unclear. To address this issue, we examined the expression pattern of various Pcdh-α isoforms in the OSNs. First, in situ hybridization histochemistry with probes for isoform-specific α11 and isoform-common αCR was performed for the OSNs of the OE. Extensive staining was observed at E16.5 for both the α11 and αCR probes (Figure 4A a, b). At P56, their expressions were widely observed in the OE, and appeared in both the immature and mature OSN cell body layers but not in the sustentacular or basal cell layers (Figure 4A c, d). In contrast to the αCR probe, the isoform-specific α11 probe showed a mosaic staining pattern (Figure 4A e). Similar mosaic patterns were observed with other α isoform-specific probes (data not shown, and see α1 in Figure 6E). The differential expression of Pcdh-α isoforms in single neurons is also observed in periglomerular cells (Kohmura et al., 1998) and mitral/tufted cells (data not shown) in the OB. These results suggested that individual OSNs and neurons in the OB differentially express Pcdh-α isoforms, similar to Purkinje cells (Esumi et al., 2005).


Constitutively expressed Protocadherin-α regulates the coalescence and elimination of homotypic olfactory axons through its cytoplasmic region.

Hasegawa S, Hirabayashi T, Kondo T, Inoue K, Esumi S, Okayama A, Hamada S, Yagi T - Front Mol Neurosci (2012)

Expression of Pcdh-α mRNAs in OSNs of the OE. (A)In situ hybridization histochemistry with an α11 isoform-specific probe and a αCR probe for all the Pcdh-α isoforms at E16.5 (a, b) and P56 (c–f). High magnifications are shown in (e) and (f). Sus, sustentacular cell-body layer; mOSN, mature OSN cell-body layer; iOSN, immature OSN cell-body layer; Basal, basal cell body layer. Scale bars, 100 μm. (B) Single cell RT-PCR analysis of individual OSNs using adult OMP-GFP mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472330&req=5

Figure 4: Expression of Pcdh-α mRNAs in OSNs of the OE. (A)In situ hybridization histochemistry with an α11 isoform-specific probe and a αCR probe for all the Pcdh-α isoforms at E16.5 (a, b) and P56 (c–f). High magnifications are shown in (e) and (f). Sus, sustentacular cell-body layer; mOSN, mature OSN cell-body layer; iOSN, immature OSN cell-body layer; Basal, basal cell body layer. Scale bars, 100 μm. (B) Single cell RT-PCR analysis of individual OSNs using adult OMP-GFP mice.
Mentions: Pcdh-α mRNAs are extensively expressed in almost all of the OSNs from E11.5 to adulthood, and Pcdh-α proteins are enriched in the OSN axons and their terminals in the glomeruli (Hasegawa et al., 2008). However, the mechanisms by which the diverse Pcdh-α family contributes to the axonal coalescence into glomeruli remain unclear. To address this issue, we examined the expression pattern of various Pcdh-α isoforms in the OSNs. First, in situ hybridization histochemistry with probes for isoform-specific α11 and isoform-common αCR was performed for the OSNs of the OE. Extensive staining was observed at E16.5 for both the α11 and αCR probes (Figure 4A a, b). At P56, their expressions were widely observed in the OE, and appeared in both the immature and mature OSN cell body layers but not in the sustentacular or basal cell layers (Figure 4A c, d). In contrast to the αCR probe, the isoform-specific α11 probe showed a mosaic staining pattern (Figure 4A e). Similar mosaic patterns were observed with other α isoform-specific probes (data not shown, and see α1 in Figure 6E). The differential expression of Pcdh-α isoforms in single neurons is also observed in periglomerular cells (Kohmura et al., 1998) and mitral/tufted cells (data not shown) in the OB. These results suggested that individual OSNs and neurons in the OB differentially express Pcdh-α isoforms, similar to Purkinje cells (Esumi et al., 2005).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: KOKORO-Biology Group and CREST-JST, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University Osaka, Japan.

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.

No MeSH data available.


Related in: MedlinePlus