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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.


Related in: MedlinePlus

Netrin-5 expression by type 2 a to type 3 cells but not by type 1 cells within the SGZ. (A–F) Triple-immunostaining of sagittal sections of adult rat brain with anti-DCX, anti-netrin-5, and anti-NeuN antibodies. DCX-positive cells in the SGZ were stained for netrin-5 as observed in confocal imaging (white arrowheads). Small populations of netrin-5-positive cells were DCX-negative, NeuN-low (black arrowhead). Please note that most of NeuN-positive cells were netrin-5 negative. (G–I) Stathmin1 and netrin-5 showed partial co-localization (white arrowheads). (J–L) Anti-Mash1 staining revealed that Mash1-positive cells express netrin-5 (white arrowheads). (M–O) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. Bar indicates 50 μm.
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Figure 6: Netrin-5 expression by type 2 a to type 3 cells but not by type 1 cells within the SGZ. (A–F) Triple-immunostaining of sagittal sections of adult rat brain with anti-DCX, anti-netrin-5, and anti-NeuN antibodies. DCX-positive cells in the SGZ were stained for netrin-5 as observed in confocal imaging (white arrowheads). Small populations of netrin-5-positive cells were DCX-negative, NeuN-low (black arrowhead). Please note that most of NeuN-positive cells were netrin-5 negative. (G–I) Stathmin1 and netrin-5 showed partial co-localization (white arrowheads). (J–L) Anti-Mash1 staining revealed that Mash1-positive cells express netrin-5 (white arrowheads). (M–O) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. Bar indicates 50 μm.

Mentions: Since DCX-positive cells showed netrin-5 immunoreactivity in the SVZ, RMS, and the GCL of the OB, we next analyzed the other major location of adult neurogenesis in rat brain, the subgranular zone (SGZ) of the hippocampal dentate gyrus (Eriksson et al., 1998). As shown in Figures 6A–C, all DCX-positive cells showed co-localization with the netrin-5 signal. In the same field, anti-NeuN staining revealed that most of netrin-5-positive cells contain undetectable or very low levels of NeuN (Figures 6D–F). This was in contrast to the OB where netrin-5 expression remained in mature neurons (Figures 5D–F). Most of netrin-5-positive cells also contain stathmin1 (Figures 6G–I), similar to that in both the SVZ and RMS. Next, we analyzed the expression of Mash1 in netrin-5-expressing cells. Consistent with the observation in both the SVZ and RMS, netrin-5 was also observed in Mash1-positive transient-amplifying cells (Figures 6J–L). Finally, we analyzed netrin-5 expression in neural stem cells (type 1 cells). Double-immunostaining for both GFAP and netrin-5 revealed that the GFAP-positive signal did not co-localize with netrin-5 (Figures 6M–O). Consistent with this result, none of the GFAP promoter-derived GFP-positive cells merged with netrin-5-positive cells (data not shown). Taken together, these results indicate netrin-5 is expressed from type-2a through to type-3 cells during adult neurogenesis in the hippocampus.


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)

Netrin-5 expression by type 2 a to type 3 cells but not by type 1 cells within the SGZ. (A–F) Triple-immunostaining of sagittal sections of adult rat brain with anti-DCX, anti-netrin-5, and anti-NeuN antibodies. DCX-positive cells in the SGZ were stained for netrin-5 as observed in confocal imaging (white arrowheads). Small populations of netrin-5-positive cells were DCX-negative, NeuN-low (black arrowhead). Please note that most of NeuN-positive cells were netrin-5 negative. (G–I) Stathmin1 and netrin-5 showed partial co-localization (white arrowheads). (J–L) Anti-Mash1 staining revealed that Mash1-positive cells express netrin-5 (white arrowheads). (M–O) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. Bar indicates 50 μm.
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Figure 6: Netrin-5 expression by type 2 a to type 3 cells but not by type 1 cells within the SGZ. (A–F) Triple-immunostaining of sagittal sections of adult rat brain with anti-DCX, anti-netrin-5, and anti-NeuN antibodies. DCX-positive cells in the SGZ were stained for netrin-5 as observed in confocal imaging (white arrowheads). Small populations of netrin-5-positive cells were DCX-negative, NeuN-low (black arrowhead). Please note that most of NeuN-positive cells were netrin-5 negative. (G–I) Stathmin1 and netrin-5 showed partial co-localization (white arrowheads). (J–L) Anti-Mash1 staining revealed that Mash1-positive cells express netrin-5 (white arrowheads). (M–O) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. Bar indicates 50 μm.
Mentions: Since DCX-positive cells showed netrin-5 immunoreactivity in the SVZ, RMS, and the GCL of the OB, we next analyzed the other major location of adult neurogenesis in rat brain, the subgranular zone (SGZ) of the hippocampal dentate gyrus (Eriksson et al., 1998). As shown in Figures 6A–C, all DCX-positive cells showed co-localization with the netrin-5 signal. In the same field, anti-NeuN staining revealed that most of netrin-5-positive cells contain undetectable or very low levels of NeuN (Figures 6D–F). This was in contrast to the OB where netrin-5 expression remained in mature neurons (Figures 5D–F). Most of netrin-5-positive cells also contain stathmin1 (Figures 6G–I), similar to that in both the SVZ and RMS. Next, we analyzed the expression of Mash1 in netrin-5-expressing cells. Consistent with the observation in both the SVZ and RMS, netrin-5 was also observed in Mash1-positive transient-amplifying cells (Figures 6J–L). Finally, we analyzed netrin-5 expression in neural stem cells (type 1 cells). Double-immunostaining for both GFAP and netrin-5 revealed that the GFAP-positive signal did not co-localize with netrin-5 (Figures 6M–O). Consistent with this result, none of the GFAP promoter-derived GFP-positive cells merged with netrin-5-positive cells (data not shown). Taken together, these results indicate netrin-5 is expressed from type-2a through to type-3 cells during adult neurogenesis in the hippocampus.

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