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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 neuroblasts and transit-amplifying cells but not by astrocytes within the RMS. (A–C) Immunostaining of sagittal sections of rat adult brain showed that most of the DCX-positive cells in the RMS stained for netrin-5 as observed in confocal imaging (white arrowheads). Some netrin-5-positive cells were DCX-negative (black arrowhead). (D–F) Stathmin1 and netrin-5 showed high co-localization (white arrowheads). (G–I) Anti-Mash1 staining revealed that Mash1-positive cells express netrin-5 (white arrowheads). (J–L) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. (M–O) Most Gfap-EGFP cells did not show netrin-5 expression. (A–L) adult rat brain and (M–O) adult Gfap-EGFP mouse brain. Bar indicates 50 μm.
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Figure 4: Netrin-5 expression by neuroblasts and transit-amplifying cells but not by astrocytes within the RMS. (A–C) Immunostaining of sagittal sections of rat adult brain showed that most of the DCX-positive cells in the RMS stained for netrin-5 as observed in confocal imaging (white arrowheads). Some netrin-5-positive cells were DCX-negative (black arrowhead). (D–F) Stathmin1 and netrin-5 showed high co-localization (white arrowheads). (G–I) Anti-Mash1 staining revealed that Mash1-positive cells express netrin-5 (white arrowheads). (J–L) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. (M–O) Most Gfap-EGFP cells did not show netrin-5 expression. (A–L) adult rat brain and (M–O) adult Gfap-EGFP mouse brain. Bar indicates 50 μm.

Mentions: Since the newly formed neuroblasts in the SVZ migrate toward the anterior region through the RMS, we next characterized the netrin-5-positive cells in the RMS. Consistent with the result in the SVZ, we found DCX-positive cells highly co-localized with the netrin-5 signal in the RMS (Figures 4A–C). In contrast to the homogeneous expression of DCX in the neuroblasts, netrin-5 was expressed at various levels in the cells. There were some netrin-5-positive cells that did not co-express DCX. On the other hand, almost all of the netrin-5-positive cells showed co-localization with stathmin1 (Figures 4D–F). Mash1-positive transit-amplifying cells were also positive for netrin-5 (Figures 4G–I), suggesting that the DCX-negative- and netrin-5-positive cells (Figures 4A–C) were transit-amplifying cells. The chains of rapidly migrating neuroblasts are ensheathed by a meshwork of GFAP-positive astrocytes, namely the “glial tube” (Lois and Alvarez-Buylla, 1994; Lois et al., 1996; Kaneko et al., 2010). Although GFAP and netrin-5 immunoreactive signals are spatially intermingled, none of the GFAP-positive signal co-localized with netrin-5 (Figures 4J–L). Since GFAP is a cytoskeletal protein and anti-GFAP antibody staining cannot visualize the entire shape of the astrocytes, we utilized GFAP promoter-controlled EGFP transgenic mice (Gfap-EGFP). As expected, most of netrin-5-positive cells are GFP-negative, confirming the mutually exclusive expression of netrin-5 and GFAP (Figures 4M–O).


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 neuroblasts and transit-amplifying cells but not by astrocytes within the RMS. (A–C) Immunostaining of sagittal sections of rat adult brain showed that most of the DCX-positive cells in the RMS stained for netrin-5 as observed in confocal imaging (white arrowheads). Some netrin-5-positive cells were DCX-negative (black arrowhead). (D–F) Stathmin1 and netrin-5 showed high co-localization (white arrowheads). (G–I) Anti-Mash1 staining revealed that Mash1-positive cells express netrin-5 (white arrowheads). (J–L) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. (M–O) Most Gfap-EGFP cells did not show netrin-5 expression. (A–L) adult rat brain and (M–O) adult Gfap-EGFP mouse brain. Bar indicates 50 μm.
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Figure 4: Netrin-5 expression by neuroblasts and transit-amplifying cells but not by astrocytes within the RMS. (A–C) Immunostaining of sagittal sections of rat adult brain showed that most of the DCX-positive cells in the RMS stained for netrin-5 as observed in confocal imaging (white arrowheads). Some netrin-5-positive cells were DCX-negative (black arrowhead). (D–F) Stathmin1 and netrin-5 showed high co-localization (white arrowheads). (G–I) Anti-Mash1 staining revealed that Mash1-positive cells express netrin-5 (white arrowheads). (J–L) Anti-GFAP staining showed that netrin-5 was not expressed in astrocytes. (M–O) Most Gfap-EGFP cells did not show netrin-5 expression. (A–L) adult rat brain and (M–O) adult Gfap-EGFP mouse brain. Bar indicates 50 μm.
Mentions: Since the newly formed neuroblasts in the SVZ migrate toward the anterior region through the RMS, we next characterized the netrin-5-positive cells in the RMS. Consistent with the result in the SVZ, we found DCX-positive cells highly co-localized with the netrin-5 signal in the RMS (Figures 4A–C). In contrast to the homogeneous expression of DCX in the neuroblasts, netrin-5 was expressed at various levels in the cells. There were some netrin-5-positive cells that did not co-express DCX. On the other hand, almost all of the netrin-5-positive cells showed co-localization with stathmin1 (Figures 4D–F). Mash1-positive transit-amplifying cells were also positive for netrin-5 (Figures 4G–I), suggesting that the DCX-negative- and netrin-5-positive cells (Figures 4A–C) were transit-amplifying cells. The chains of rapidly migrating neuroblasts are ensheathed by a meshwork of GFAP-positive astrocytes, namely the “glial tube” (Lois and Alvarez-Buylla, 1994; Lois et al., 1996; Kaneko et al., 2010). Although GFAP and netrin-5 immunoreactive signals are spatially intermingled, none of the GFAP-positive signal co-localized with netrin-5 (Figures 4J–L). Since GFAP is a cytoskeletal protein and anti-GFAP antibody staining cannot visualize the entire shape of the astrocytes, we utilized GFAP promoter-controlled EGFP transgenic mice (Gfap-EGFP). As expected, most of netrin-5-positive cells are GFP-negative, confirming the mutually exclusive expression of netrin-5 and GFAP (Figures 4M–O).

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