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Drosophila astrocytes cover specific territories of the CNS neuropil and are instructed to differentiate by Prospero, a key effector of Notch.

Accepted version
Peer-reviewed

Repository DOI


Type

Article

Change log

Authors

Peco, Emilie 
Davla, Sejal 
Camp, Darius 
Stacey, Stephanie M 

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.

Description

Keywords

Astrocyte development, Astroglial map, Notch, Pointed, Prospero, Animals, Astrocytes, Cell Lineage, Central Nervous System, DNA-Binding Proteins, Drosophila Proteins, Drosophila melanogaster, Excitatory Amino Acid Transporter 1, Excitatory Amino Acid Transporter 2, Gene Expression Regulation, Developmental, Nerve Tissue Proteins, Neurogenesis, Neuroglia, Neuropil, Nuclear Proteins, Proto-Oncogene Proteins, RNA Interference, RNA, Small Interfering, Receptors, Notch, Transcription Factors

Journal Title

Development

Conference Name

Journal ISSN

0950-1991
1477-9129

Volume Title

143

Publisher

The Company of Biologists
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/I022414/1)
This work was supported by grants from the Canadian Institutes of Health Research (CIHR) and the Canada Foundation for Innovation (CFI) to D.J.v.M.; by a Biotechnology and Biological Sciences Research Council (UK) grant [BB/I022414/1] to M.L.; and by studentship awards to S.D. from McGill University (Max Stern) and the Integrated Program in Neuroscience.