Temporarily Epigenetic Repression in Bergmann Glia Regulates the Migration of Granule Cells. Issue 10 (22nd March 2021)

• Record Type: Journal Article
• Authors: Chen, Shaoxuan; Zhang, Kunkun; Zhang, Boxin; Jiang, Mengyun; Zhang, Xue; Guo, Yi; Yu, Yingying; Qin, Tianyu; Li, Hongda; Chen, Qiang; Cai, Zhiyu; Luo, Site; Huang, Yi; Hu, Jin; Mo, Wei
• Is Part Of: Advanced science. Volume 8:Issue 10(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-03-22
• Subjects: Bergmann glia -- BG development -- ECM -- GC migration -- H3K9me3 -- Nfix -- Setdb1; Science -- Periodicals; 505
• DOI: 10.1002/advs.202003164
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Forming tight interaction with both Purkinje and granule cells (GCs), Bergmann glia (BG) are essential for cerebellar morphogenesis and neuronal homeostasis. However, how BG act in this process is unclear without comprehensive transcriptome landscape of BG. Here, high temporal‐resolution investigation of transcriptomes with FACS‐sorted BG revealed the dynamic expression of genes within given functions and pathways enabled BG to assist neural migration and construct neuron‐glia network. It is found that the peak time of GCs migration (P7‐10) strikingly coincides with the downregulation of extracellular matrix (ECM) related genes, and the disruption of which by Setdb1 ablation at P7‐10 in BG leads to significant migration defect of GCs emphasizing the criticality of Nfix‐Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GCs migration in vivo. Thus, BG's transcriptomic landscapes offer an insight into the mechanism by which BG are in depth integrated in cerebellar neural network. Abstract : Functional cerebellum relays on the coordinated spatiotemporal interplay between neurons and glia. The remarkable down‐regulation of components of ECM is critical for GCs migration at very narrow time window (P7–P10), and transcription factor Nfix recruits Setdb1, a tri‐methyltransferase of H3K9 to load H3K9me3 modification on ECM genes that should be repressed in BG at P7–P10.