Limits...
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

Expression of netrin-5 in the SVZ of adult rat brain. (A–C) Immunostaining of sagittal sections of adult rat brain revealed that DCX-positive cells in the SVZ stained for netrin-5 as observed in confocal imaging (white arrowheads). Some netrin-5-positive cells were DCX-negative (black arrowheads). (D–F) Stathmin1 and netrin-5 showed high co-localization (white arrowheads). (G–I) Mash1-positive cells are also netrin-5-positive (white arrowheads). (J–L) Netrin-5 expression did not co-localize with GFAP. Bar indicates 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4403520&req=5

Figure 3: Expression of netrin-5 in the SVZ of adult rat brain. (A–C) Immunostaining of sagittal sections of adult rat brain revealed that DCX-positive cells in the SVZ stained for netrin-5 as observed in confocal imaging (white arrowheads). Some netrin-5-positive cells were DCX-negative (black arrowheads). (D–F) Stathmin1 and netrin-5 showed high co-localization (white arrowheads). (G–I) Mash1-positive cells are also netrin-5-positive (white arrowheads). (J–L) Netrin-5 expression did not co-localize with GFAP. Bar indicates 50 μm.

Mentions: In the adult SVZ, a subset of the astrocyte-like cells (type B cells) are proliferative stem cells that generate neuroblasts (type A cells) via transit-amplifying cells (type C cells). The majority of netrin-5 immunoreactive cells in the SVZ showed a morphology typical of the chain-forming neuroblasts. In order to determine the netrin-5-expressing cell types in the SVZ, we performed double-immunolabeling in a sagittal section of the rat adult brain using antibodies against netrin-5 and DCX, a microtubule binding protein widely used as a marker for neuroblasts (Zhao et al., 2008). As shown in Figures 3A–C, all DCX-positive cells at the SVZ co-expressed netrin-5. There were some netrin-5-positive SVZ cells that did not co-express DCX, suggesting that netrin-5 expression is initiated in DCX-negative type C cells. We also stained for the microtubule binding protein stathmin1, which is expressed in the SVZ cells, including neuroblasts (Camoletto et al., 1997; Jin et al., 2004). Double immunostaining showed complete co-localization of stathmin1 and netrin-5 (Figures 3D–F). Since stathmin1 expression is regulated by Mash1 (Ascl1) (Yamada et al., 2010), we then evaluated netrin-5 expression in Mash1-positive transit-amplifying cells (Figures 3G–I). As a result, all Mash1 positive cells were netrin-5 positive, indicating that transit-amplifying cells also express netrin-5 (Figures 3G–I). Next, we determined whether netrin-5 expression occurs in type B cells. Netrin-5 was not detected in GFAP-positive cells (type-B cells or other astrocytes; Figures 3J–L). Taken together, these results suggest that netrin-5 is expressed in transit-amplifying cells and in neuroblasts but not in either neural stem cells or astrocytes in the SVZ.


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 SVZ of adult rat brain. (A–C) Immunostaining of sagittal sections of adult rat brain revealed that DCX-positive cells in the SVZ stained for netrin-5 as observed in confocal imaging (white arrowheads). Some netrin-5-positive cells were DCX-negative (black arrowheads). (D–F) Stathmin1 and netrin-5 showed high co-localization (white arrowheads). (G–I) Mash1-positive cells are also netrin-5-positive (white arrowheads). (J–L) Netrin-5 expression did not co-localize with GFAP. Bar indicates 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Expression of netrin-5 in the SVZ of adult rat brain. (A–C) Immunostaining of sagittal sections of adult rat brain revealed that DCX-positive cells in the SVZ stained for netrin-5 as observed in confocal imaging (white arrowheads). Some netrin-5-positive cells were DCX-negative (black arrowheads). (D–F) Stathmin1 and netrin-5 showed high co-localization (white arrowheads). (G–I) Mash1-positive cells are also netrin-5-positive (white arrowheads). (J–L) Netrin-5 expression did not co-localize with GFAP. Bar indicates 50 μm.
Mentions: In the adult SVZ, a subset of the astrocyte-like cells (type B cells) are proliferative stem cells that generate neuroblasts (type A cells) via transit-amplifying cells (type C cells). The majority of netrin-5 immunoreactive cells in the SVZ showed a morphology typical of the chain-forming neuroblasts. In order to determine the netrin-5-expressing cell types in the SVZ, we performed double-immunolabeling in a sagittal section of the rat adult brain using antibodies against netrin-5 and DCX, a microtubule binding protein widely used as a marker for neuroblasts (Zhao et al., 2008). As shown in Figures 3A–C, all DCX-positive cells at the SVZ co-expressed netrin-5. There were some netrin-5-positive SVZ cells that did not co-express DCX, suggesting that netrin-5 expression is initiated in DCX-negative type C cells. We also stained for the microtubule binding protein stathmin1, which is expressed in the SVZ cells, including neuroblasts (Camoletto et al., 1997; Jin et al., 2004). Double immunostaining showed complete co-localization of stathmin1 and netrin-5 (Figures 3D–F). Since stathmin1 expression is regulated by Mash1 (Ascl1) (Yamada et al., 2010), we then evaluated netrin-5 expression in Mash1-positive transit-amplifying cells (Figures 3G–I). As a result, all Mash1 positive cells were netrin-5 positive, indicating that transit-amplifying cells also express netrin-5 (Figures 3G–I). Next, we determined whether netrin-5 expression occurs in type B cells. Netrin-5 was not detected in GFAP-positive cells (type-B cells or other astrocytes; Figures 3J–L). Taken together, these results suggest that netrin-5 is expressed in transit-amplifying cells and in neuroblasts but not in either neural stem cells or astrocytes in the SVZ.

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