Mechanisms underlying microglial colonization of developing neural retina in zebrafish

Microglia are brain-resident macrophages that function as the first line of defense in brain. Embryonic microglial precursors originate in peripheral mesoderm and migrate into brain during development. However, the mechanism by which they colonize the brain is incompletely understood. The retina is one of the first brain regions to accommodate microglia. In zebrafish, embryonic microglial precursors use intraocular hyaloid blood vessels as a pathway to migrate into the optic cup via the choroid fissure. Once retinal progenitor cells exit from the cell cycle, microglial precursors associated with hyaloid blood vessels start to infiltrate the retina preferentially through neurogenic regions, suggesting that colonization of retinal tissue depends upon the neurogenic state. Upstream of blood vessels and retinal neurogenesis, IL34 also promotes microglial precursor colonization of the retina. Altogether, CSF receptor signaling, blood vessels, and neuronal differentiation, function as guidance cues, and create an essential path for microglial migration into developing retina.