PT  - JOURNAL ARTICLE
AU  - Damisah, Eyiyemisi C.
AU  - Hill, Robert A.
AU  - Rai, Anupama
AU  - Chen, Fuyi
AU  - Rothlin, Carla V.
AU  - Ghosh, Sourav
AU  - Grutzendler, Jaime
TI  - Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo
AID  - 10.1126/sciadv.aba3239
DP  - 2020 Jun 01
TA  - Science Advances
PG  - eaba3239
VI  - 6
IP  - 26
4099  - http://advances.sciencemag.org/content/6/26/eaba3239.short
4100  - http://advances.sciencemag.org/content/6/26/eaba3239.full
SO  - Sci Adv2020 Jun 01; 6
AB  - Cell death is prevalent throughout life; however, the coordinated interactions and roles of phagocytes during corpse removal in the live brain are poorly understood. We developed photochemical and viral methodologies to induce death in single cells and combined this with intravital optical imaging. This approach allowed us to track multicellular phagocytic interactions with precise spatiotemporal resolution. Astrocytes and microglia engaged with dying neurons in an orchestrated and synchronized fashion. Each glial cell played specialized roles: Astrocyte processes rapidly polarized and engulfed numerous small dendritic apoptotic bodies, while microglia migrated and engulfed the soma and apical dendrites. The relative involvement and phagocytic specialization of each glial cell was plastic and controlled by the receptor tyrosine kinase Mertk. In aging, there was a marked delay in apoptotic cell removal. Thus, a precisely orchestrated response and cross-talk between glial cells during corpse removal may be critical for maintaining brain homeostasis.