{Reference Type}: Journal Article
{Title}: A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages.
{Author}: Brioschi S;Belk JA;Peng V;Molgora M;Rodrigues PF;Nguyen KM;Wang S;Du S;Wang WL;Grajales-Reyes GE;Ponce JM;Yuede CM;Li Q;Baer JM;DeNardo DG;Gilfillan S;Cella M;Satpathy AT;Colonna M;
{Journal}: Immunity
{Volume}: 56
{Issue}: 5
{Year}: 05 2023 9
{Factor}: 43.474
{DOI}: 10.1016/j.immuni.2023.01.028
{Abstract}: Genetic tools to target microglia specifically and efficiently from the early stages of embryonic development are lacking. We generated a constitutive Cre line controlled by the microglia signature gene Crybb1 that produced nearly complete recombination in embryonic brain macrophages (microglia and border-associated macrophages [BAMs]) by the perinatal period, with limited recombination in peripheral myeloid cells. Using this tool in combination with Flt3-Cre lineage tracer, single-cell RNA-sequencing analysis, and confocal imaging, we resolved embryonic-derived versus monocyte-derived BAMs in the mouse cortex. Deletion of the transcription factor SMAD4 in microglia and embryonic-derived BAMs using Crybb1-Cre caused a developmental arrest of microglia, which instead acquired a BAM specification signature. By contrast, the development of genuine BAMs remained unaffected. Our results reveal that SMAD4 drives a transcriptional and epigenetic program that is indispensable for the commitment of brain macrophages to the microglia fate and highlight Crybb1-Cre as a tool for targeting embryonic brain macrophages.