Age-specific function of α5β1 integrin in microglial migration during early colonization of the developing mouse cortex
Résumé
Microglia, the immune cells of the central nervous system, 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 development, microglial migration
speed 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 of
matrix–integrin interactions during microglial migration in the embryonic brain ex vivo. We focused
on microglia–fibronectin interactions mediated through the fibronectin receptor a5b1 integrin
because in vitro work indirectly suggested a role for this ligand–receptor pair. Using 2-photon
time-lapse microscopy on acute ex vivo embryonic brain slices, we found that migration occurs in a
saltatory pattern and is developmentally regulated. Most importantly, there is an age-specific function
of the a5b1 integrin during microglial cortex colonization. At embryonic day (E) 13.5, a5b1
facilitates migration while from E15.5, it inhibits migration. These results indicate a developmentally
regulated function of a5b1 integrin in microglial migration during colonization of the
embryonic brain.