CNS macrophages differentially rely on an intronic Csf1r enhancer for their development

Journal article (2020)

Authors

David A.D. Munro The University of Edinburgh
Barry M. Bradford The University of Edinburgh
Samanta A. Mariani The University of Edinburgh
David W. Hampton The University of Edinburgh
C.S. Vink The University of Edinburgh
Siddharthan Chandran The University of Edinburgh
David A. Hume University of Queensland
Clare Pridans The University of Edinburgh
Josef Priller Charité Universittsmedizin Berlin, The University of Edinburgh
Affiliation
External organisation
Cerebrospinal fluid Cerebral ventricles CNS-associated macrophages Kolmer cells Myeloid cells Phagocytes
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Published Date

2020

Language

English

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Abstract

The 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.