title: Developmental Apoptosis Mediates Entry and Positioning of Microglia in the Zebrafish Brain.
abstract: In the brain, neurons that fail to assemble into functional circuits are eliminated. Their clearance depends on microglia, immune cells that colonize the CNS during embryogenesis. Despite the importance of these cells in development and disease, the mechanisms that target and position microglia within the brain are unclear. Here we show that, in zebrafish, attraction of microglia into the brain exploits differences in developmental neuronal apoptosis and that these provide a mechanism for microglial distribution. Reducing neuronal cell death results in fewer microglia, whereas increased apoptosis enhances brain colonization, resulting in more microglia at later stages. Interestingly, attraction into the brain depends on nucleotide signaling, the same signaling system used to guide microglia toward brain injuries. Finally, this work uncovers a cell-non-autonomous role for developmental apoptosis. Classically considered a wasteful process, programmed cell death is exploited here to configure the immune-neuronal interface of the brain.
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Alessandra Maria
authors.initials: AM
authors.lastname: Casano
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Marvin
authors.initials: M
authors.lastname: Albert
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany. Electronic address: peri@embl.de.
authors.forename: Francesca
authors.initials: F
authors.lastname: Peri
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D001930:Brain Injuries / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D017628:Microglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015027:Zebrafish / Q000502:physiology*