Mechanisms underlying microglial colonization of developing neural retina in zebrafish.

Nishtha Ranawat,Ichiro Masai

doi:10.7554/elife.70550

Nishtha Ranawat, Ichiro Masai

Open Access

https://doi.org/10.7554/elife.70550

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Abstract

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 the 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 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. Along with blood vessels and retinal neurogenesis, IL34 also participates in microglial precursor colonization of the retina. Altogether, CSF receptor signaling, blood vessels, and neuronal differentiation function as cues to create an essential path for microglial migration into developing retina.

Highlights

Microglia are the resident macrophages of brain
Embryonic microglial precursors progressively colonize developing zebrafish retina In zebrafish, early macrophages are generated from myeloid cells originating in the rostral blood island (RBI) around 11 hpf and these macrophages colonize the brain and retina by 55 hpf (Xu et al, 2015)
Early macrophages outside the brain never express apolipoprotein E (apo E) (Herbomel et al, 2001), suggesting that only brain and retina-resident macrophages give rise to microglia

Summary

Introduction

Microglia are the resident macrophages of brain. These dedicated CNS phagocytes form the innate immune system of embryonic and adult brain. Microglia eliminate cellular debris to prevent neuro- inflammation and to promote neuronal protection in vertebrates (Ashwell, 1991; Calderó et al, 2009; Lawson et al, 1990; Neumann et al, 2009; Sierra et al, 2010). They prune unnecessary synapses to establish functional, mature neural circuits during brain development, performing a variety of cellular functions (Paolicelli et al, 2011; Tremblay et al, 2010).

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