非表示:
キーワード:
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要旨:
The central nervous system has developed immune surveillance to protect its environment. This surveillance is primarily a resident and morphologically distinct cell population, the microglia. Microglia colonize the brain very early during development as highly migratory macrophages with an extraordinary capacity to penetrate tissues in the absence of infection. Up to date, the migration and the transition of macrophages into microglia have not been observed or studied in vivo and the underlying molecular mechanisms are still largely unknown. Danio rerio (zebrafish) is an ideal model system to identify required molecules via large forward genetic screens. By screening, we identified several classes of mutants in which either brain colonization or transition of macrophages into microglia is affected. We are in the process of identifying several of the underlying genes. Furthermore, we have generated several zebrafish transgenic lines in which the GFP marker is under the control of tissue specific promoters that drive its expression in migrating macrophages and/or differentiated microglia. Because the early embryo is optically transparent, we were able to observe macrophages in living embryos and to gain novel insights into the mechanisms of brain colonization and microglial function in vivo. Moreover, the availability of these GFP reporter lines facilitates the characterization of the mutant phenotypes by allowing us to analyze the in vivo function of the newly identified genes in the context of the living embryo.
