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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

Ectopic glomeruli in MOR28 and P2 OSN projections. (A) Representative examples of the lateral side of three MOR28 glomeruli, (a: one innate glomerulus, e and i: two small ectopic glomeruli). (b, f, and j) Immunoreactivity for bassoon (a presynaptic active-zone protein) was observed in all the MOR28 glomeruli in the PcdhaΔCR/ΔCR mice. (c, g, and k) merged images. (d, h, and l) DAPI. Scale bar, 100 μm. (B) Lateral P2 glomeruli in whole-mount OBs from WT (a) and PcdhaΔCR2/ΔCR2 (b) mice at P7. In the PcdhaΔCR2/ΔCR2 mice, small ectopic glomeruli were observed near the large main glomerulus. Scale bars, 500 μm.
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Figure 1: Ectopic glomeruli in MOR28 and P2 OSN projections. (A) Representative examples of the lateral side of three MOR28 glomeruli, (a: one innate glomerulus, e and i: two small ectopic glomeruli). (b, f, and j) Immunoreactivity for bassoon (a presynaptic active-zone protein) was observed in all the MOR28 glomeruli in the PcdhaΔCR/ΔCR mice. (c, g, and k) merged images. (d, h, and l) DAPI. Scale bar, 100 μm. (B) Lateral P2 glomeruli in whole-mount OBs from WT (a) and PcdhaΔCR2/ΔCR2 (b) mice at P7. In the PcdhaΔCR2/ΔCR2 mice, small ectopic glomeruli were observed near the large main glomerulus. Scale bars, 500 μm.

Mentions: The diverse Pcdh-α family is required for the normal coalescence of OSN axons into glomeruli and for the elimination of ectopic glomeruli in the OB. In Pcdh-α-deficient mice, abnormal, small ectopic glomeruli are observed for OSNs expressing the M71, M72, and MOR23 ORs (Hasegawa et al., 2008). To confirm whether Pcdh-α is involved in the axonal coalescence of homotypic OSNs in the glomeruli in ventral and dorsal positions of the OB, we examined the axonal coalescence of OSNs expressing the ORs MOR28 (ventral side) and mOR-EG (dorsal side). The glomerular position of MOR28, but not of mOR-EG, is greatly influenced by the disruption of Neuropilin-2 or Plexin-A3 (Takeuchi et al., 2010). The disruption of BIG-2 impairs the axonal coalescence of MOR28 and mOR-EG OSNs to different degrees (Kaneko-Goto et al., 2008). Immunostaining with OR-specific antibodies showed increased numbers of glomeruli in the OSNs at P30 in the Pcdh-α-deficient (PcdhaΔCR/ΔCR) vs. wild-type (WT) mice, for mOR-EG (averages, lateral 1.6 vs. 1.0; medial 1.4 vs. 1.0, respectively) and MOR28 (lateral 2.4 vs. 1.2; medial 1.3 vs. 1.0) (Table 1, Figure 1A), similar to the previous results for M71, M72, and MOR23 (Hasegawa et al., 2008).


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)

Ectopic glomeruli in MOR28 and P2 OSN projections. (A) Representative examples of the lateral side of three MOR28 glomeruli, (a: one innate glomerulus, e and i: two small ectopic glomeruli). (b, f, and j) Immunoreactivity for bassoon (a presynaptic active-zone protein) was observed in all the MOR28 glomeruli in the PcdhaΔCR/ΔCR mice. (c, g, and k) merged images. (d, h, and l) DAPI. Scale bar, 100 μm. (B) Lateral P2 glomeruli in whole-mount OBs from WT (a) and PcdhaΔCR2/ΔCR2 (b) mice at P7. In the PcdhaΔCR2/ΔCR2 mice, small ectopic glomeruli were observed near the large main glomerulus. Scale bars, 500 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Ectopic glomeruli in MOR28 and P2 OSN projections. (A) Representative examples of the lateral side of three MOR28 glomeruli, (a: one innate glomerulus, e and i: two small ectopic glomeruli). (b, f, and j) Immunoreactivity for bassoon (a presynaptic active-zone protein) was observed in all the MOR28 glomeruli in the PcdhaΔCR/ΔCR mice. (c, g, and k) merged images. (d, h, and l) DAPI. Scale bar, 100 μm. (B) Lateral P2 glomeruli in whole-mount OBs from WT (a) and PcdhaΔCR2/ΔCR2 (b) mice at P7. In the PcdhaΔCR2/ΔCR2 mice, small ectopic glomeruli were observed near the large main glomerulus. Scale bars, 500 μm.
Mentions: The diverse Pcdh-α family is required for the normal coalescence of OSN axons into glomeruli and for the elimination of ectopic glomeruli in the OB. In Pcdh-α-deficient mice, abnormal, small ectopic glomeruli are observed for OSNs expressing the M71, M72, and MOR23 ORs (Hasegawa et al., 2008). To confirm whether Pcdh-α is involved in the axonal coalescence of homotypic OSNs in the glomeruli in ventral and dorsal positions of the OB, we examined the axonal coalescence of OSNs expressing the ORs MOR28 (ventral side) and mOR-EG (dorsal side). The glomerular position of MOR28, but not of mOR-EG, is greatly influenced by the disruption of Neuropilin-2 or Plexin-A3 (Takeuchi et al., 2010). The disruption of BIG-2 impairs the axonal coalescence of MOR28 and mOR-EG OSNs to different degrees (Kaneko-Goto et al., 2008). Immunostaining with OR-specific antibodies showed increased numbers of glomeruli in the OSNs at P30 in the Pcdh-α-deficient (PcdhaΔCR/ΔCR) vs. wild-type (WT) mice, for mOR-EG (averages, lateral 1.6 vs. 1.0; medial 1.4 vs. 1.0, respectively) and MOR28 (lateral 2.4 vs. 1.2; medial 1.3 vs. 1.0) (Table 1, Figure 1A), similar to the previous results for M71, M72, and MOR23 (Hasegawa et al., 2008).

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