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Netrin-5 is highly expressed in neurogenic regions of the adult brain.

Yamagishi S, Yamada K, Sawada M, Nakano S, Mori N, Sawamoto K, Sato K - Front Cell Neurosci (2015)

Bottom Line: In the OB, netrin-5 expression was maintained in neuroblasts, but its level was decreased in NeuN-positive mature neurons.In the hippocampal SGZ, netrin-5 was observed in Mash1-positive cells and in DCX-positive neuroblasts, but not in GFAP-positive astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3 cells.These data suggest that netrin-5 is produced by both transit-amplifying cells and neuroblasts to control neurogenesis in the adult brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neuroscience, Hamamatsu University School of Medicine Hamamatsu, Shizuoka, Japan.

ABSTRACT
Mammalian netrin family proteins are involved in targeting of axons, neuronal migration, and angiogenesis and act as repulsive and attractive guidance molecules. Netrin-5 is a new member of the netrin family with homology to the C345C domain of netrin-1. Unlike other netrin proteins, murine netrin-5 consists of two EGF motifs of the laminin V domain (LE) and the C345C domain, but lacks the N-terminal laminin VI domain and one of the three LE motifs. We generated a specific antibody against netrin-5 to investigate its expression pattern in the rodent adult brain. Strong netrin-5 expression was observed in the olfactory bulb (OB), rostral migrate stream (RMS), the subventricular zone (SVZ), and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, where neurogenesis occurs in the adult brain. In the SVZ and RMS, netrin-5 expression was observed in Mash1-positive transit-amplifying cells and in Doublecortin (DCX)-positive neuroblasts, but not in GFAP-positive astrocytes. In the OB, netrin-5 expression was maintained in neuroblasts, but its level was decreased in NeuN-positive mature neurons. In the hippocampal SGZ, netrin-5 was observed in Mash1-positive cells and in DCX-positive neuroblasts, but not in GFAP-positive astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3 cells. These data suggest that netrin-5 is produced by both transit-amplifying cells and neuroblasts to control neurogenesis in the adult brain.

No MeSH data available.


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Expression of netrin-5 in the GCL of the OB in the adult brain. (A–F) Triple-immunostaining of sagittal sections of adult rat brain using anti-DCX, anti-netrin-5, and anti-NeuN antibodies. Netrin-5 was highly expressed in Dcx+ neuroblasts (white arrowheads), Dcx+NeuN+ immature neurons (white arrows), and a subset of NeuN+ mature neurons (black arrowheads), and decreased but still detectable in most NeuN+ mature neurons. (G–I) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. (J–L) Gfap-EGFP cells did not show netrin-5 expression. (A–I) adult rat brain and (J–L) adult Gfap-EGFP mouse brain. Bar indicates 50 μm.
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Figure 5: Expression of netrin-5 in the GCL of the OB in the adult brain. (A–F) Triple-immunostaining of sagittal sections of adult rat brain using anti-DCX, anti-netrin-5, and anti-NeuN antibodies. Netrin-5 was highly expressed in Dcx+ neuroblasts (white arrowheads), Dcx+NeuN+ immature neurons (white arrows), and a subset of NeuN+ mature neurons (black arrowheads), and decreased but still detectable in most NeuN+ mature neurons. (G–I) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. (J–L) Gfap-EGFP cells did not show netrin-5 expression. (A–I) adult rat brain and (J–L) adult Gfap-EGFP mouse brain. Bar indicates 50 μm.

Mentions: The migrated neuroblasts are differentiated into GABAergic neurons and integrated in the GCL of the OB (Abrous et al., 2005). Since the strong immunoreactivity of netrin-5 was observed in the GCL (Figure 2B), we attempted to determine the cell type in the GCL. The netrin-5 signal was observed in the cell body and in the basal part of the apical dendrites of the DCX-positive new neurons (Figures 5A–C). Since only about 20% of the netrin-5-positive cells in the GCL co-expressed DCX, we next analyzed whether netrin-5 expression is present in mature neurons. As expected, the DCX-negative- and netrin-5-positive cells were NeuN-positive, indicating that netrin-5 is also expressed in mature GCs (Figures 5D–F). The expression level of Netrin-5 is stronger in the DCX-positive cells than that in the NeuN-positive cells, suggesting that netrin-5 expression is decreased during the maturation process. Consistent with the exclusive expression of GFAP and netrin-5 in both the SVZ and RMS, we could not observe co-localization of GFAP and netrin-5 in the GCL of the OB (Figures 5G–L), indicating that netrin-5 is not expressed by astrocytes.


Netrin-5 is highly expressed in neurogenic regions of the adult brain.

Yamagishi S, Yamada K, Sawada M, Nakano S, Mori N, Sawamoto K, Sato K - Front Cell Neurosci (2015)

Expression of netrin-5 in the GCL of the OB in the adult brain. (A–F) Triple-immunostaining of sagittal sections of adult rat brain using anti-DCX, anti-netrin-5, and anti-NeuN antibodies. Netrin-5 was highly expressed in Dcx+ neuroblasts (white arrowheads), Dcx+NeuN+ immature neurons (white arrows), and a subset of NeuN+ mature neurons (black arrowheads), and decreased but still detectable in most NeuN+ mature neurons. (G–I) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. (J–L) Gfap-EGFP cells did not show netrin-5 expression. (A–I) adult rat brain and (J–L) adult Gfap-EGFP mouse brain. Bar indicates 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403520&req=5

Figure 5: Expression of netrin-5 in the GCL of the OB in the adult brain. (A–F) Triple-immunostaining of sagittal sections of adult rat brain using anti-DCX, anti-netrin-5, and anti-NeuN antibodies. Netrin-5 was highly expressed in Dcx+ neuroblasts (white arrowheads), Dcx+NeuN+ immature neurons (white arrows), and a subset of NeuN+ mature neurons (black arrowheads), and decreased but still detectable in most NeuN+ mature neurons. (G–I) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. (J–L) Gfap-EGFP cells did not show netrin-5 expression. (A–I) adult rat brain and (J–L) adult Gfap-EGFP mouse brain. Bar indicates 50 μm.
Mentions: The migrated neuroblasts are differentiated into GABAergic neurons and integrated in the GCL of the OB (Abrous et al., 2005). Since the strong immunoreactivity of netrin-5 was observed in the GCL (Figure 2B), we attempted to determine the cell type in the GCL. The netrin-5 signal was observed in the cell body and in the basal part of the apical dendrites of the DCX-positive new neurons (Figures 5A–C). Since only about 20% of the netrin-5-positive cells in the GCL co-expressed DCX, we next analyzed whether netrin-5 expression is present in mature neurons. As expected, the DCX-negative- and netrin-5-positive cells were NeuN-positive, indicating that netrin-5 is also expressed in mature GCs (Figures 5D–F). The expression level of Netrin-5 is stronger in the DCX-positive cells than that in the NeuN-positive cells, suggesting that netrin-5 expression is decreased during the maturation process. Consistent with the exclusive expression of GFAP and netrin-5 in both the SVZ and RMS, we could not observe co-localization of GFAP and netrin-5 in the GCL of the OB (Figures 5G–L), indicating that netrin-5 is not expressed by astrocytes.

Bottom Line: In the OB, netrin-5 expression was maintained in neuroblasts, but its level was decreased in NeuN-positive mature neurons.In the hippocampal SGZ, netrin-5 was observed in Mash1-positive cells and in DCX-positive neuroblasts, but not in GFAP-positive astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3 cells.These data suggest that netrin-5 is produced by both transit-amplifying cells and neuroblasts to control neurogenesis in the adult brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neuroscience, Hamamatsu University School of Medicine Hamamatsu, Shizuoka, Japan.

ABSTRACT
Mammalian netrin family proteins are involved in targeting of axons, neuronal migration, and angiogenesis and act as repulsive and attractive guidance molecules. Netrin-5 is a new member of the netrin family with homology to the C345C domain of netrin-1. Unlike other netrin proteins, murine netrin-5 consists of two EGF motifs of the laminin V domain (LE) and the C345C domain, but lacks the N-terminal laminin VI domain and one of the three LE motifs. We generated a specific antibody against netrin-5 to investigate its expression pattern in the rodent adult brain. Strong netrin-5 expression was observed in the olfactory bulb (OB), rostral migrate stream (RMS), the subventricular zone (SVZ), and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, where neurogenesis occurs in the adult brain. In the SVZ and RMS, netrin-5 expression was observed in Mash1-positive transit-amplifying cells and in Doublecortin (DCX)-positive neuroblasts, but not in GFAP-positive astrocytes. In the OB, netrin-5 expression was maintained in neuroblasts, but its level was decreased in NeuN-positive mature neurons. In the hippocampal SGZ, netrin-5 was observed in Mash1-positive cells and in DCX-positive neuroblasts, but not in GFAP-positive astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3 cells. These data suggest that netrin-5 is produced by both transit-amplifying cells and neuroblasts to control neurogenesis in the adult brain.

No MeSH data available.


Related in: MedlinePlus