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ISL1通过Shh信号通路调节肺部分支的形态发生
Ruiqi Huang1, Chujing Zhang1, Yuting Zheng1
1Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, People's Republic of China.
The Journal of biological chemistry
|July 13, 2023
概括
表皮岛1 (Isl1) 对于肺部发育至关重要. 切除Isl1通过降低Shh信号的调节来破坏肺部分支和叶片形成,突出其在肺形态发生过程中表皮质-介质细胞通信中的作用.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 肺部分支形态发生是一种复杂的过程,涉及复杂的信号通路.
- 转录因子在协调肺形成等发育过程中起着至关重要的作用.
研究的目的:
- 为了研究LIM主体基因转录因子Islet1 (Isl1) 在肺上皮细胞发育中的作用.
- 阐明Isl1调节肺分支形态发生的分子机制.
主要方法:
- 使用ShhCre小鼠模型在肺上皮层中切除Islet1.
- 基因表达分析的RNA测序 (RNA-Seq) 和现场杂交.
- 染色体免疫沉 (ChIP) 试验以确定直接的转录标.
- 刺通道的激活,以拯救发育缺陷.
主要成果:
- 皮质Isl1切除导致肺部有缺陷的分支和不完整的叶片形成.
- 在ISL1缺陷的肺部中观察到中酶体细胞增殖的减少.
- 包括Shh和Sox9在内的关键发育基因被下调.
- Isl1直接与SHH上皮质增强剂 (MACS1) 结合,表明SHH是直接的目标.
- 刺通路的激活挽救了观察到的肺部发育缺陷.
结论:
- 表皮岛1对于调节肺部分支形态发生是必不可少的.
- Isl1通过调节Shh信号来控制肺部的发育,该信号调节了表皮细胞与介质细胞之间的通信.
- 这些发现揭示了Isl1在控制肺形成的遗传网络中的关键作用.
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