PMID- 37708022 OWN - NLM STAT- Publisher LR - 20231004 IS - 2211-1247 (Electronic) VI - 42 IP - 9 DP - 2023 Sep 26 TI - Organization of Purkinje cell development by neuronal MEGF11 in cerebellar granule cells. PG - 113137 LID - S2211-1247(23)01149-X [pii] LID - 10.1016/j.celrep.2023.113137 [doi] AB - As cerebellar granule cells (GCs) coordinate the formation of regular cerebellar networks during postnatal development, molecules in GCs are expected to be involved. Here, we test the effects of the knockdown (KD) of multiple epidermal growth factor-like domains protein 11 (MEGF11), which is a homolog of proteins mediating astrocytic phagocytosis but is substantially increased at the later developmental stages of GCs on cerebellar development. MEGF11-KD in GCs of developing mice results in abnormal cerebellar structures, including extensively ectopic Purkinje cell (PC) somas, and in impaired motor functions. MEGF11-KD also causes abnormally asynchronous synaptic release from GC axons, parallel fibers, before the appearance of abnormal cerebellar structures. Interestingly, blockade of this abnormal synaptic release restores most of the cerebellar structures. Thus, apart from phagocytic functions of its related homologs in astrocytes, MEGF11 in GCs promotes proper PC development and cerebellar network formation by regulating immature synaptic transmission. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Jun, Soyoung AU - Jun S AD - Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea. FAU - Kim, Muwoong AU - Kim M AD - Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea. FAU - Park, Heeyoun AU - Park H AD - Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea. FAU - Hwang, Eunmi AU - Hwang E AD - Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea. FAU - Yamamoto, Yukio AU - Yamamoto Y AD - Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea. Electronic address: yukio.kist@gmail.com. FAU - Tanaka-Yamamoto, Keiko AU - Tanaka-Yamamoto K AD - Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea. Electronic address: keikoyamat@gmail.com. LA - eng PT - Journal Article DEP - 20230913 PL - United States TA - Cell Rep JT - Cell reports JID - 101573691 SB - IM OTO - NOTNLM OT - CP: Neuroscience OT - MEGF11 OT - Purkinje cell soma alignment OT - cerebellar granule cell OT - climbing fiber synapse formation OT - migration OT - motor coordination OT - shRNA-mediated knockdown OT - synchronous neurotransmitter release COIS- Declaration of interests The authors declare no competing interests. EDAT- 2023/09/14 18:43 MHDA- 2023/09/14 18:43 CRDT- 2023/09/14 12:35 PHST- 2023/02/14 00:00 [received] PHST- 2023/07/24 00:00 [revised] PHST- 2023/08/31 00:00 [accepted] PHST- 2023/09/14 18:43 [pubmed] PHST- 2023/09/14 18:43 [medline] PHST- 2023/09/14 12:35 [entrez] AID - S2211-1247(23)01149-X [pii] AID - 10.1016/j.celrep.2023.113137 [doi] PST - ppublish SO - Cell Rep. 2023 Sep 26;42(9):113137. doi: 10.1016/j.celrep.2023.113137. Epub 2023 Sep 13.