caa a22 4500 606176020 CHVBK 20210128100745.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00018-014-1789-7 doi (NATIONALLICENCE)springer-10.1007/s00018-014-1789-7 MANF silencing, immunity induction or autophagy trigger an unusual cell type in metamorphosing Drosophila brain [Elektronische Daten] [Vassilis Stratoulias, Tapio Heino] Glia are abundant cells in the brain of animals ranging from flies to humans. They perform conserved functions not only in neural development and wiring, but also in brain homeostasis. Here we show that by manipulating gene expression in glia, a previously unidentified cell type appears in the Drosophila brain during metamorphosis. More specifically, this cell type appears in three contexts: (1) after the induction of either immunity, or (2) autophagy, or (3) by silencing of neurotrophic factor DmMANF in glial cells. We call these cells MANF immunoreactive Cells (MiCs). MiCs are migratory based on their shape, appearance in brain areas where no cell bodies exist and the nuclear localization of dSTAT. They are labeled with a unique set of molecular markers including the conserved neurotrophic factor DmMANF and the transcription factor Zfh1. They possess the nuclearly localized protein Relish, which is the hallmark of immune response activation. They also express the conserved engulfment receptor Draper, therefore indicating that they are potentially phagocytic. Surprisingly, they do not express any of the common glial and neuronal markers. In addition, ultrastructural studies show that MiCs are extremely rich in lysosomes. Our findings reveal critical molecular and functional components of an unusual cell type in the Drosophila brain. We suggest that MiCs resemble macrophages/hemocytes and vertebrate microglia based on their appearance in the brain upon genetically challenged conditions and the expression of molecular markers. Interestingly, macrophages/hemocytes or microglia-like cells have not been reported in the fly nervous system before. The Author(s), 2014 Pupa nationallicence Tor nationallicence IMD nationallicence Atg nationallicence APF : After puparium formation nationallicence CNS : Central nervous systems nationallicence DA : Dopaminergic nationallicence ER : Endoplasmic reticulum nationallicence MiC : Manf immunoreactive cell nationallicence PH3 : Phosphorylated histone 3 nationallicence RNAi : RNA interference nationallicence TEM : Transmission electron microscopy nationallicence TLR : Toll-like receptor nationallicence TNF : Tumor necrosis factor nationallicence Tor : Target of rapamycin nationallicence Stratoulias Vassilis Department of Biosciences, University of Helsinki, Viikinkaari 5, P.O. Box 56, 00014, Helsinki, Finland aut Heino Tapio Department of Biosciences, University of Helsinki, Viikinkaari 5, P.O. Box 56, 00014, Helsinki, Finland aut Cellular and Molecular Life Sciences Springer Basel 72/10(2015-05-01), 1989-2004 1420-682X 72:10<1989 2015 72 18 https://doi.org/10.1007/s00018-014-1789-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1789-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Stratoulias Vassilis Department of Biosciences, University of Helsinki, Viikinkaari 5, P.O. Box 56, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Heino Tapio Department of Biosciences, University of Helsinki, Viikinkaari 5, P.O. Box 56, 00014, Helsinki, Finland aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/10(2015-05-01), 1989-2004 1420-682X 72:10<1989 2015 72 18