title: Drosophila astrocytes cover specific territories of the CNS neuropil and are instructed to differentiate by Prospero, a key effector of Notch.
abstract: Astrocytes are crucial in the formation, fine-tuning, function and plasticity of neural circuits in the central nervous system. However, important questions remain about the mechanisms instructing astrocyte cell fate. We have studied astrogenesis in the ventral nerve cord of Drosophila larvae, where astrocytes exhibit remarkable morphological and molecular similarities to those in mammals. We reveal the births of larval astrocytes from a multipotent glial lineage, their allocation to reproducible positions, and their deployment of ramified arbors to cover specific neuropil territories to form a stereotyped astroglial map. Finally, we unraveled a molecular pathway for astrocyte differentiation in which the Ets protein Pointed and the Notch signaling pathway are required for astrogenesis; however, only Notch is sufficient to direct non-astrocytic progenitors toward astrocytic fate. We found that Prospero is a key effector of Notch in this process. Our data identify an instructive astrogenic program that acts as a binary switch to distinguish astrocytes from other glial cells.
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3G 1A4 Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4.
authors.forename: Emilie
authors.initials: E
authors.lastname: Peco
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3G 1A4 McGill Integrated Program in Neuroscience McGill University, Montreal, Quebec, Canada H3A 2B4.
authors.forename: Sejal
authors.initials: S
authors.lastname: Davla
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3G 1A4 Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada H3A 1A3.
authors.forename: Darius
authors.initials: D
authors.lastname: Camp
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3G 1A4 McGill Integrated Program in Neuroscience McGill University, Montreal, Quebec, Canada H3A 2B4.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Stacey
authors.affiliation: Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.
authors.forename: Matthias
authors.initials: M
authors.lastname: Landgraf
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3G 1A4 Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 don.vanmeyel@mcgill.ca.
authors.forename: Don J
authors.initials: DJ
authors.lastname: van Meyel
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D019070:Cell Lineage / Q000502:physiology; D002490:Central Nervous System / Q000196:embryology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology*; D027341:Excitatory Amino Acid Transporter 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009457:Neuroglia / Q000166:cytology; D019581:Neuropil / Q000166:cytology*; D009687:Nuclear Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C421004:Eaat2 protein, Drosophila; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; C497759:N protein, Drosophila; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D014157:Transcription Factors; C116191:e protein, Drosophila; C083884:pnt protein, Drosophila; C073099:pros protein, Drosophila; C076560:H protein, Drosophila
keywords: Astrocyte development; Astroglial map; Notch; Pointed; Prospero