RRC ID 64374
著者 Kim T, Shin H, Song B, Won C, Yoshida H, Yamaguchi M, Cho KS, Lee IS.
タイトル Overexpression of H3K36 methyltransferase NSD in glial cells affects brain development in Drosophila.
ジャーナル Glia
Abstract NSD1 is a histone methyltransferase that methylates the lysine 36 at histone H3. NSD duplication is associated with short stature, microcephaly, intellectual disability, and behavioral defects in humans. Ectopic overexpression of NSD, an NSD1 homolog in Drosophila, was shown to induce developmental abnormalities via apoptosis. In this study, to investigate the effects of NSD overexpression on Drosophila brain development, we first examined the typical NSD expression pattern in larval brains and found that endogenous NSD promoter activity was detected only in subsets of glial cells. Pan-glial, but not pan-neuronal, NSD overexpression induced apoptosis in larval brain cells. However, pan-glial NSD overexpression also induced caspase-3 cleavage in neuronal cells. Among the various glial cell types, NSD overexpression in only astrocytic glia induced apoptosis and abnormal learning defects in the larval stage. Furthermore, NSD overexpression downregulated the expression of various astrocyte-specific genes, including draper (drpr), possibly owing to an indirect effect of NSD overexpression-induced astrocytic apoptosis. Since drpr plays a role in axon pruning during mushroom body (MB) formation in Drosophila astrocytes, we examined the effect of astrocytic NSD overexpression on this process and found that it disrupted the clearance of γ-neurons in the MB, subsequently inducing arrhythmic locomotor activity of the fly. Thus, these results suggest that aberrant NSD overexpression may cause neurodevelopmental disorders by interfering with crucial functions of astrocytes in the brain, underlining the importance of the tightly controlled astrocytic NSD expression for proper neurodevelopment.
巻・号 68(12)
ページ 2503-2516
公開日 2020-12-1
DOI 10.1002/glia.23867
PMID 32531091
MeSH Animals Brain / metabolism Drosophila* / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism Methyltransferases Neuroglia / metabolism
IF 5.984
リソース情報
ショウジョウバエ DGRC#103953 DGRC#112830 DGRC#105188 DGRC#105240