PMID- 36790930 OWN - NLM STAT- MEDLINE DCOM- 20231005 LR - 20231005 IS - 2211-1247 (Electronic) VI - 42 IP - 2 DP - 2023 Feb 28 TI - Actin-dependent astrocytic infiltration is a key step for axon defasciculation during remodeling. PG - 112117 LID - S2211-1247(23)00128-6 [pii] LID - 10.1016/j.celrep.2023.112117 [doi] LID - 112117 AB - Astrocytes are essential for synapse formation, maturation, and plasticity; however, their function during developmental neuronal remodeling is largely unknown. To identify astrocytic molecules required for axon pruning of mushroom body (MB) gamma neurons in Drosophila, we profiled astrocytes before (larva) and after (adult) remodeling. Focusing on genes enriched in larval astrocytes, we identified 12 astrocytic genes that are required for axon pruning, including the F-actin regulators Actin-related protein 2/3 complex, subunit 1 (Arpc1) and formin3 (form3). Interestingly, perturbing astrocytic actin dynamics does not affect their gross morphology, migration, or transforming growth factor beta (TGF-beta) secretion. In contrast, actin dynamics is required for astrocyte infiltration into the axon bundle at the onset of pruning. Remarkably, decreasing axonal adhesion facilitates infiltration by Arpc1 knockdown (KD) astrocytes and promotes axon pruning. Conversely, increased axonal adhesion reduces lobe infiltration by wild-type (WT) astrocytes. Together, our findings suggest that actin-dependent astrocytic infiltration is a key step in axon pruning, thus promoting our understanding of neuron-glia interactions during remodeling. CI - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Marmor-Kollet, Neta AU - Marmor-Kollet N AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot 7610001, Israel. FAU - Berkun, Victoria AU - Berkun V AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel. FAU - Cummings, Gideon AU - Cummings G AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel. FAU - Keren-Shaul, Hadas AU - Keren-Shaul H AD - Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel. FAU - David, Eyal AU - David E AD - Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel. FAU - Addadi, Yoseph AU - Addadi Y AD - Weizmann Institute of Science, Life Sciences Core Facilities, Rehovot 7610001, Israel. FAU - Schuldiner, Oren AU - Schuldiner O AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: oren.schuldiner@weizmann.ac.il. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230214 PL - United States TA - Cell Rep JT - Cell reports JID - 101573691 RN - 0 (Actins) RN - 0 (Drosophila Proteins) SB - IM MH - Animals MH - *Actins/metabolism MH - Astrocytes/metabolism MH - Axons/metabolism MH - Drosophila/metabolism MH - *Drosophila Proteins/genetics/metabolism MH - Neurons/metabolism PMC - PMC9989824 OTO - NOTNLM OT - CP: Cell biology OT - CP: Neuroscience OT - RNA-seq OT - actin dynamics OT - astrocytes OT - axon adhesion OT - axon pruning OT - drosophila OT - glia OT - mushroom body OT - neuro-glia interactions OT - neuronal remodeling COIS- Declaration of interests The authors declare that they have no conflict of interest. EDAT- 2023/02/16 06:00 MHDA- 2023/10/04 06:43 PMCR- 2023/02/14 CRDT- 2023/02/15 12:37 PHST- 2021/12/15 00:00 [received] PHST- 2022/10/17 00:00 [revised] PHST- 2023/01/28 00:00 [accepted] PHST- 2023/10/04 06:43 [medline] PHST- 2023/02/16 06:00 [pubmed] PHST- 2023/02/15 12:37 [entrez] PHST- 2023/02/14 00:00 [pmc-release] AID - S2211-1247(23)00128-6 [pii] AID - 112117 [pii] AID - 10.1016/j.celrep.2023.112117 [doi] PST - ppublish SO - Cell Rep. 2023 Feb 28;42(2):112117. doi: 10.1016/j.celrep.2023.112117. Epub 2023 Feb 14.