Link to Pubmed [PMID] – 32973110
Link to DOI – jcs.24903710.1242/jcs.249037
J Cell Sci 2020 Oct 22; 133(20):jcs249037
Most tissues harbor a substantial population of resident macrophages. Here we elucidate a functional link between the Slc7a7 cationic amino acid transporter and tissue macrophages. We identified a mutant zebrafish devoid of microglia due to a mutation in the slc7a7 gene. We found that in Slc7a7 deficient larvae, macrophages do enter the retina and brain to become microglia, but then die during the developmental wave of neuronal apoptosis, which triggers intense efferocytic work from them. A similar macrophage demise occurs at other tissues and stages where macrophages have to engulf many cell corpses, whether due to developmental or experimentally triggered cell death. We found that Slc7a7 is the main cationic amino acid transporter expressed in macrophages of zebrafish larvae, and that its expression is induced in tissue macrophages within 1-2 hrs upon efferocytosis. Our data indicate that Slc7a7 is vital not only for microglia but also for any steadily efferocytic tissue macrophages, and that slc7a7 gene induction is one of the adaptive responses that allow them to cope with the catabolism of numerous dead cells without compromising their own viability.
The retinal macrophage number in a Slc7a7-deficient larva was similar to the control at the onset of the imaging, but then steadily decreased, to virtually zero by 15 h later.
Research highlight in JCS issue 133: https://jcs.biologists.org/content/133/20/e2003