| First Author | Yu HL | Year | 2024 |
| Journal | Int J Mol Sci | Volume | 25 |
| Issue | 13 | PubMed ID | 39000184 |
| Mgi Jnum | J:351386 | Mgi Id | MGI:7702547 |
| Doi | 10.3390/ijms25137079 | Citation | Yu HL, et al. (2024) Netrin-1 Is an Important Mediator in Microglia Migration. Int J Mol Sci 25(13) |
| abstractText | Microglia migrate to the cerebral cortex during early embryonic stages. However, the precise mechanisms underlying microglia migration remain incompletely understood. As an extracellular matrix protein, Netrin-1 is involved in modulating the motility of diverse cells. In this paper, we found that Netrin-1 promoted microglial BV2 cell migration in vitro. Mechanism studies indicated that the activation of GSK3beta activity contributed to Netrin-1-mediated microglia migration. Furthermore, Integrin alpha6/beta1 might be the relevant receptor. Single-cell data analysis revealed the higher expression of Integrin alpha6 subunit and beta1 subunit in microglia in comparison with classical receptors, including Dcc, Neo1, Unc5a, Unc5b, Unc5c, Unc5d, and Dscam. Microscale thermophoresis (MST) measurement confirmed the high binding affinity between Integrin alpha6/beta1 and Netrin-1. Importantly, activation of Integrin alpha6/beta1 with IKVAV peptides mirrored the microglia migration and GSK3 activation induced by Netrin-1. Finally, conditional knockout (CKO) of Netrin-1 in radial glial cells and their progeny led to a reduction in microglia population in the cerebral cortex at early developmental stages. Together, our findings highlight the role of Netrin-1 in microglia migration and underscore its therapeutic potential in microglia-related brain diseases. |
