...
首页> 外文期刊>Journal of Experimental Neuroscience >Single-Cell Transcriptomics Reveals Regulators of Neuronal Migration and Maturation During Brain Development:
【24h】

Single-Cell Transcriptomics Reveals Regulators of Neuronal Migration and Maturation During Brain Development:

机译:单细胞转录组学揭示了大脑发育过程中神经元迁移和成熟的调节剂:

获取原文
           

摘要

The correct establishment of inhibitory circuits is crucial for cortical functionality and defects during the development of γ-aminobutyric acid–expressing cortical interneurons contribute to the pathophysiology of psychiatric disorders. A critical developmental step is the migration of cortical interneurons from their site of origin within the subpallium to the cerebral cortex, orchestrated by intrinsic and extrinsic signals. In addition to genetic networks, epigenetic mechanisms such as DNA methylation by DNA methyltransferases (DNMTs) are suggested to drive stage-specific gene expression underlying developmental processes. The mosaic structure of the interneuron generating domains producing a variety of interneurons for diverse destinations complicates research on regulatory instances of cortical interneuron migration. To this end, we performed single-cell transcriptome analysis revealing Dnmt1 expression in subsets of migrating interneurons. We found that DNMT1 preserves the migratory morphology in part through transcriptional control over Pak6 that promotes neurite complexity in postmigratory cells. In addition, we identified Ccdc184, a gene of unknown function, to be highly expressed in postmitotic interneurons. Single-cell mRNA sequencing revealed a positive correlation of Ccdc184 with cell adhesion–associated genes pointing to potential implications of CCDC184 in processes relying on cell-cell adhesion–like migration or morphological differentiation of interneurons that deserves further investigations.
机译:正确建立抑制回路对于表达γ-氨基丁酸的皮质中间神经元的发育过程中的皮质功能和缺陷至关重要,这有助于精神疾病的病理生理。关键的发展步骤是由内在和外在信号精心策划,使皮质神经元从其在皮下层内部的起源位置迁移至大脑皮质。除了遗传网络外,还提出了表观遗传机制,例如通过DNA甲基转移酶(DNMT)进行DNA甲基化,以驱动发育过程中特定阶段的基因表达。中间神经元产生域的镶嵌结构产生了用于不同目的地的多种中间神经元,这使得对皮质中间神经元迁移的调控实例的研究变得复杂。为此,我们进行了单细胞转录组分析,揭示了Dnmt1在迁移的中间神经元子集中的表达。我们发现,DNMT1保留了迁移形态,部分是通过对Pak6的转录控制来实现的,该控制可促进迁移后细胞中的神经突复杂性。此外,我们确定了功能未知的基因Ccdc184在有丝分裂后的神经元中高表达。单细胞mRNA测序显示,Ccdc184与细胞粘附相关基因呈正相关,这表明CCDC184在依赖细胞粘附的过程(如中间神经元的迁移或形态分化)中具有潜在的意义,值得进一步研究。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号