Age-specific function of α5β1 integrin in microglial migration during early colonization of the developing mouse cortex

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Smolders, Sophie Marie-Thérèse | Swinnen, Nina | Kessels, Sofie | Arnauts, Kaline | Smolders, Silke | Le Bras, Barbara | Rigo, Jean-Michel | Legendre, Pascal | Brône, Bert

Edité par CCSD ; Wiley -

International audience. Microglia, the immune cells of the central nervous system, take part in brain development andhomeostasis. They derive from primitive myeloid progenitors that originate in the yolk sac and colonizethe brain mainly through intensive migration. During development, microglial migrationspeed declines which suggests that their interaction with the microenvironment changes. However,the matrix–cell interactions allowing dispersion within the parenchyma are unknown.Therefore, we aimed to better characterize the migration behavior and to assess the role ofmatrix–integrin interactions during microglial migration in the embryonic brain ex vivo. We focusedon microglia–fibronectin interactions mediated through the fibronectin receptor a5b1 integrinbecause in vitro work indirectly suggested a role for this ligand–receptor pair. Using 2-photontime-lapse microscopy on acute ex vivo embryonic brain slices, we found that migration occurs in asaltatory pattern and is developmentally regulated. Most importantly, there is an age-specific functionof the a5b1 integrin during microglial cortex colonization. At embryonic day (E) 13.5, a5b1facilitates migration while from E15.5, it inhibits migration. These results indicate a developmentallyregulated function of a5b1 integrin in microglial migration during colonization of theembryonic brain.

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