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.
Highlights
Netrin family proteins are diffusible axon guidance molecules
We show that netrin-5 is strongly expressed in neuroproliferative regions, namely in the subventricular zone (SVZ) and subgranular zone (SGZ)
Netrin-5 Homology to Netrin-1 In order to search for a new axon guidance protein homologs to murine netrin-1, we performed protein BLAST analysis with the mouse netrin-1 C345C domain (472-601 aa), which is partially involved in binding to the Unc5 receptor (Kruger et al, 2004)
Summary
Netrin family proteins are diffusible axon guidance molecules. Originally netrin-1 was identified as a chemical attractant for spinal commissural axons during embryonic development (Serafini et al, 1994, 1996). Inhibiting DCC by an antibody disrupted the direction of the migrating chain of cells Another netrin-1 receptor, neogenin, is known to be expressed in both neuroblasts and GFAP-positive astrocytes in the RMS of both rodents and humans (Bradford et al, 2010). Netrin-5 is co-expressed with Mash, DCX, and stathmin, which regulates microtubule stability, in neuroblasts in both the SVZ and RMS, whereas GFAP-positive cells do not co-express netrin-5. Consistent with these findings, Mash1-positive cells and DCX-positive neuroblasts in the SGZ co-expressed netrin-5, indicating netrin-5 expression occurs from type 2a to type 3 cells. These expression patterns suggest that netrin-5 plays a role in adult neurogenesis
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