Limits...
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 glomerulus-like structures of P2-expressing OSNs in neonatal PcdhaΔCR2/ΔCR2 mice found by whole-mount observation. (A) X-gal-stained P2 glomeruli in the P0 OBs of WT (a, b) or PcdhaΔCR2/ΔCR2 (c, d) mice. In PcdhaΔCR2/ΔCR2 mice, abnormal axonal projections from the olfactory nerve were often detected (arrowheads). Scale bars, 500 μm. (B) Double staining with an anti-OMP antibody and DAPI in the P0 OBs in coronal sections of WT (a, b) or PcdhaΔCR/ΔCR (c, d) mice. Scale bar, 100 μm. (C) Immunostaining with an anti-VGluT2 antibody in the lateral (a, b) and medial (c, d) sides of the P0 OBs in WT (a, c) or PcdhaΔCR/ΔCR (b, d) mice. Scale bar, 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3472330&req=5

Figure 3: Ectopic glomerulus-like structures of P2-expressing OSNs in neonatal PcdhaΔCR2/ΔCR2 mice found by whole-mount observation. (A) X-gal-stained P2 glomeruli in the P0 OBs of WT (a, b) or PcdhaΔCR2/ΔCR2 (c, d) mice. In PcdhaΔCR2/ΔCR2 mice, abnormal axonal projections from the olfactory nerve were often detected (arrowheads). Scale bars, 500 μm. (B) Double staining with an anti-OMP antibody and DAPI in the P0 OBs in coronal sections of WT (a, b) or PcdhaΔCR/ΔCR (c, d) mice. Scale bar, 100 μm. (C) Immunostaining with an anti-VGluT2 antibody in the lateral (a, b) and medial (c, d) sides of the P0 OBs in WT (a, c) or PcdhaΔCR/ΔCR (b, d) mice. Scale bar, 100 μm.

Mentions: As described above, the Pcdh-α-deficient mice had multiple, small, extraneous glomeruli for all the OSN axons examined. These ectopic glomeruli persist until adulthood (Hasegawa et al., 2008). To determine whether the abnormalities in the Pcdh-α-deficient olfactory system resulted primarily from an inability of homotypic OSN axons to coalesce, we next analyzed the formation of glomeruli during early development using mice from crosses between M71-IRES-taulacZ or P2-IRES-taulacZ and WT or PcdhaΔCR/ΔCR mice (Hasegawa et al., 2008). The glomerular structures are initiated on embryonic day (E) 15–16, when both OSN fibers and mitral cell dendrites contribute to the formation of glomerulus-like structures (Blanchart et al., 2006). In the PcdhaΔCR/ΔCR mice, we observed some stray marked fibers that projected to inappropriate regions distant from the target site, and many more M71 and P2 glomerulus-like structures than in WT mice, even on postnatal day 0 (P0) (arrowheads in Figures 2A, 3A).


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 glomerulus-like structures of P2-expressing OSNs in neonatal PcdhaΔCR2/ΔCR2 mice found by whole-mount observation. (A) X-gal-stained P2 glomeruli in the P0 OBs of WT (a, b) or PcdhaΔCR2/ΔCR2 (c, d) mice. In PcdhaΔCR2/ΔCR2 mice, abnormal axonal projections from the olfactory nerve were often detected (arrowheads). Scale bars, 500 μm. (B) Double staining with an anti-OMP antibody and DAPI in the P0 OBs in coronal sections of WT (a, b) or PcdhaΔCR/ΔCR (c, d) mice. Scale bar, 100 μm. (C) Immunostaining with an anti-VGluT2 antibody in the lateral (a, b) and medial (c, d) sides of the P0 OBs in WT (a, c) or PcdhaΔCR/ΔCR (b, d) mice. Scale bar, 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Ectopic glomerulus-like structures of P2-expressing OSNs in neonatal PcdhaΔCR2/ΔCR2 mice found by whole-mount observation. (A) X-gal-stained P2 glomeruli in the P0 OBs of WT (a, b) or PcdhaΔCR2/ΔCR2 (c, d) mice. In PcdhaΔCR2/ΔCR2 mice, abnormal axonal projections from the olfactory nerve were often detected (arrowheads). Scale bars, 500 μm. (B) Double staining with an anti-OMP antibody and DAPI in the P0 OBs in coronal sections of WT (a, b) or PcdhaΔCR/ΔCR (c, d) mice. Scale bar, 100 μm. (C) Immunostaining with an anti-VGluT2 antibody in the lateral (a, b) and medial (c, d) sides of the P0 OBs in WT (a, c) or PcdhaΔCR/ΔCR (b, d) mice. Scale bar, 100 μm.
Mentions: As described above, the Pcdh-α-deficient mice had multiple, small, extraneous glomeruli for all the OSN axons examined. These ectopic glomeruli persist until adulthood (Hasegawa et al., 2008). To determine whether the abnormalities in the Pcdh-α-deficient olfactory system resulted primarily from an inability of homotypic OSN axons to coalesce, we next analyzed the formation of glomeruli during early development using mice from crosses between M71-IRES-taulacZ or P2-IRES-taulacZ and WT or PcdhaΔCR/ΔCR mice (Hasegawa et al., 2008). The glomerular structures are initiated on embryonic day (E) 15–16, when both OSN fibers and mitral cell dendrites contribute to the formation of glomerulus-like structures (Blanchart et al., 2006). In the PcdhaΔCR/ΔCR mice, we observed some stray marked fibers that projected to inappropriate regions distant from the target site, and many more M71 and P2 glomerulus-like structures than in WT mice, even on postnatal day 0 (P0) (arrowheads in Figures 2A, 3A).

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