Visualizing Microglia with a Fluorescence Turn‐On Ugt1a7c Substrate

Microglia, the brain‐resident macrophage, are involved in brain development and contribute to the progression of neural disorders. Despite the importance of microglia, imaging of live microglia at a cellular resolution has been limited to transgenic mice. Efforts have therefore been dedicated to developing new methods for microglia detection and imaging. Using a thorough structure–activity relationships study, we developed CDr20, a high‐performance fluorogenic chemical probe that enables the visualization of microglia both in vitro and in vivo. Using a genome‐scale CRISPR‐Cas9 knockout screen, the UDP‐glucuronosyltransferase Ugt1a7c was identified as the target of CDr20. The glucuronidation of CDr20 by Ugt1a7c in microglia produces fluorescence. Lightbulb moment: The fluorogenic probe, CDr20, specifically labels mouse microglia both in vitro and in vivo, enabling their visualization through a fluorescence turn‐on response, mediated by the UDP‐glucuronosyltransferase, Ugt1a7c. CDr20 could be useful for the characterization of the role of microglia during brain development and the pathogenesis of neural disorders.