CNS macrophages differentially rely on an intronicCsf1renhancer for their development

David A D Munro,Samanta A Mariani,Barry M Bradford,David A Hume,Siddharthan Chandran,Chris S Vink,Clare Pridans,Josef Priller,David W Hampton

doi:10.1242/dev.194449

Abstract

ABSTRACTThe central nervous system hosts parenchymal macrophages, known as microglia, and non-parenchymal macrophages, collectively termed border-associated macrophages (BAMs). Microglia, but not BAMs, were reported to be absent in mice lacking a conserved Csf1r enhancer: the fms-intronic regulatory element (FIRE). However, it is unknown whether FIRE deficiency also impacts BAM arrival and/or maintenance. Here, we show that macrophages in the ventricular system of the brain, including Kolmer's epiplexus macrophages, are absent in Csf1rΔFIRE/ΔFIRE mice. Stromal choroid plexus BAMs are also considerably reduced. During normal development, we demonstrate that intracerebroventricular macrophages arrive from embryonic day 10.5, and can traverse ventricular walls in embryonic slice cultures. In Csf1rΔFIRE/ΔFIRE embryos, the arrival of both primitive microglia and intracerebroventricular macrophages was eliminated, whereas the arrival of cephalic mesenchyme and stromal choroid plexus BAMs was only partially restricted. Our results provide new insights into the development and regulation of different CNS macrophage populations.

Highlights

Macrophages are present throughout the central nervous system (CNS)
We show that microglia and intracerebroventricular macrophages are dependent on fms-intronic regulatory element (FIRE), whereas cephalic mesenchyme and stromal choroid plexus (ChP) border-associated macrophages (BAMs) are only partially reliant
Intracerebroventricular and ChP macrophages differentially depend on FIRE during adulthood In the initial organism-wide characterisation of adult Csf1rΔFIRE/ΔFIRE mice (Rojo et al, 2019), microglia were absent from brains, whereas BAMs were seemingly maintained

Summary

Introduction

Intracerebroventricular and ChP macrophages differentially depend on FIRE during adulthood In the initial organism-wide characterisation of adult Csf1rΔFIRE/ΔFIRE mice (Rojo et al, 2019), microglia were absent from brains, whereas BAMs were seemingly maintained. We show that IBA1+ macrophages (epiplexus, supraependymal and free-floating macrophages) were entirely absent in both the lateral and third ventricles of adult Csf1rΔFIRE/ΔFIRE mice, but present in both Csf1r+/+ and Csf1r+/ΔFIRE controls (red arrowheads; Fig. 1A-C).

Results

Conclusion