Vascular Lamb1 guides the migration of retinal microglial precursors via Itga6-Rac1 signaling

Retinal microglia originate during embryonic hematopoiesis and play an essential role in visual function. However, the mechanisms guiding microglial precursors into the retina remain poorly understood. Here, we show that, in zebrafish embryos, microglial precursors enter the vitreous space via blood vessels, mainly the ventral radial vessel/hyaloid vein, before migrating to the developing retina. Vascular Lamb1 provides a haptotactic gradient sensed by Itga6 in microglial precursors, which activates Rac1 signaling to promote F-actin polarization and directional migration. Disruption of blood vessels or interference with the Lamb1-Itga6 axis blocks microglial precursor entry into the vitreous space and reduces retinal colonization. Similarly, LAMB1 is deposited in the blood vessels of mice, and endothelial-specific deficiency impairs microglial precursor settlement. These findings indicate a conserved Lamb1-Itga6 signaling axis that guides retinal microglial migration during development.