Beta1 integrins control microglial migration in an age-specific manner during embryonic neurodevelopment.

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Brône, Bert | Smolders, Sophie Marie-Thérèse | Swinnen, Nina | Kessels, Sofie | K, Arnouts | Smolders, Steven | Le Bras, Barbara | Rigo, Jean-Michel | Legendre, Pascal

Edité par CCSD -

International audience. Microglia, the brain phagocytes, take part in brain development and homeostasis. They derive from primitive myeloid progenitors that originate in the yolk sac and colonize the brain mainly through intensive migration. During cortical development, the microglial migration speed declines, which suggests a change in interaction with the microenvironment during embryogenesis. However, the mechanisms allowing dispersion within the parenchyma are unclear. Recent evidence points to a functional role of microglia-fibronectin interactions for migration. α5β1 integrins contribute to the microglia-fibronectin interactions during migration in the developing neocortex on embryonic day (E) 13.5, 15.5 and 17.5. Using blocking antibodies in 2-photon time-lapse microscopy on acute brain slices, we reveal a surprising age-specific regulation of α5β1 function during embryonic microglial cortex colonization. At E13.5, α5β1 blockage inhibits while from E15.5, it promotes migration. α5β1 integrin does however not seem to play a role in mediating contact between microglia and blood vessels. General β1 blockage, targeting microglial interactions with extracellular matrix molecules such as laminin and vitronectin besides fibronectin, suggests opposing roles for other integrin subtypes in mediating migration from E15.5 onwards.

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