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Publication : Organization of Purkinje cell development by neuronal MEGF11 in cerebellar granule cells.

First Author  Jun S Year  2023
Journal  Cell Rep Volume  42
Issue  9 Pages  113137
PubMed ID  37708022 Mgi Jnum  J:350453
Mgi Id  MGI:7663299 Doi  10.1016/j.celrep.2023.113137
Citation  Jun S, et al. (2023) Organization of Purkinje cell development by neuronal MEGF11 in cerebellar granule cells. Cell Rep 42(9):113137
abstractText  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.
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