A genetic program for vascular pericyte precursors

Abstract

AbstractBrain pericytes are critical for regulating endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. The genetic pathways guiding undifferentiated cells into mature pericytes are not well understood. We show here that precursor populations from both neural crest and head mesoderm express the transcription factornkx3.1develop into brain pericytes. We identify the gene signature of these precursors, and show that annkx3.1, foxf2a, andcxcl12b-expressing pericyte precursor population is present around the basilar artery prior to artery formation and pericyte recruitment. The precursors later spread throughout the brain and differentiate to express canonical pericyte markers. Cxcl12b-Cxcr4 signaling is required for pericyte attachment and differentiation. Further, bothnkx3.1andcxcl12b are necessary and sufficient in regulating pericyte number as loss inhibits and gain increases pericyte number. Through genetic experiments we have defined a precursor population for brain pericytes and identified genes critical for their differentiation.