CNS macrophages differentially rely on an intronicCsf1renhancer for their development

• DOI: 10.1242/dev.194449
• Publication Date: 2020-12-16T22:16:11Z
• Authors: David A. D. Munro; Barry M. Bradford; Samanta A. Mariani; David W. Hampton; Chris S. Vink; Siddharthan Chandran; David A. Hume; Clare Pridans; Josef Priller
• Keywords: Research Report; Central Nervous System; 0301 basic medicine; Macrophages; Brain; Embryonic Development; Regulatory Sequences, Nucleic Acid; Embryo, Mammalian; Introns; 3. Good health; Mice; 03 medical and health sciences; Enhancer Elements, Genetic; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Animals; Microglia; Parenchymal Tissue

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.