Scholarlink

Background <p>IntS11, the core catalytic subunit of the Integrator (INT), functions in various stages of transcription. However, its specific function in orchestrating neural lineage progression remains poorly understood.</p> Results <p>Using a Drosophila model, we found that the absence of IntS11 leads to reduced brain size, which is not attributable to neuroblast (NB) loss or apoptosis but is due to impaired NB proliferation. MARCM (mosaic analysis with a repressible cell marker) revealed impaired clonal expansion, characterized by a significant decrease in progeny cell number. Live imaging and FUCCI analysis further confirmed a G1 arrest in IntS11-deficient NBs. Single-cell RNA-seq revealed downregulation of cell cycle regulators (<i>aurB</i>, <i>CycE</i>, <i>Cdk4</i>) in NBs and differentiation genes in GMCs, which were confirmed as candidates by ChIP-qPCR. Approximately 80% of neuronal morphogenesis–associated genes exhibiting 3′UTR shortening were downregulated. We further established that IntS11 physically binds to these loci to maintain lengthened 3′UTR isoforms and ensure mRNA stability in larval brains.</p> Conclusions <p>Collectively, our findings establish IntS11 as a stage-specific regulator of neural lineage progression that sustains NB proliferation through transcriptional control of cell-cycle genes and stabilizes differentiation programs by maintaining long 3′UTR isoforms.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Integrator subunit IntS11 orchestrates the temporal dynamics of neural lineage progression in Drosophila

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月25日

查看全文
  • Qiao Xiao,
  • Liqiang Ai,
  • Boquan Jia,
  • Mengjia Kuang,
  • Shengwei Xiao,
  • Xiaoxue Bi,
  • Yingbao Zhu,
  • Guangxu Li,
  • Wen Huang,
  • Ranhui Duan

摘要

Background

IntS11, the core catalytic subunit of the Integrator (INT), functions in various stages of transcription. However, its specific function in orchestrating neural lineage progression remains poorly understood.

Results

Using a Drosophila model, we found that the absence of IntS11 leads to reduced brain size, which is not attributable to neuroblast (NB) loss or apoptosis but is due to impaired NB proliferation. MARCM (mosaic analysis with a repressible cell marker) revealed impaired clonal expansion, characterized by a significant decrease in progeny cell number. Live imaging and FUCCI analysis further confirmed a G1 arrest in IntS11-deficient NBs. Single-cell RNA-seq revealed downregulation of cell cycle regulators (aurB, CycE, Cdk4) in NBs and differentiation genes in GMCs, which were confirmed as candidates by ChIP-qPCR. Approximately 80% of neuronal morphogenesis–associated genes exhibiting 3′UTR shortening were downregulated. We further established that IntS11 physically binds to these loci to maintain lengthened 3′UTR isoforms and ensure mRNA stability in larval brains.

Conclusions

Collectively, our findings establish IntS11 as a stage-specific regulator of neural lineage progression that sustains NB proliferation through transcriptional control of cell-cycle genes and stabilizes differentiation programs by maintaining long 3′UTR isoforms.