Temporal requirements for ISL1 in sympathetic neuron proliferation, differentiation, and diversification.
Temporal requirements for ISL1 in sympathetic neuron proliferation, differentiation, and diversification.
复制标题
Isl1 在交感神经元增殖、分化和多样化中的时间需求
DOI：
10.1038/s41419-018-0283-9
复制
发表时间：
2018-02-14
影响因子：
9
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Zhang Q;Huang R;Ye Y;Guo X;Lu J;Zhu F;Gong X;Zhang Q;Yan J;Luo L;Zhuang S;Chen Y;Zhao X;Evans SM;Jiang C;Liang X;Sun Y
交感神经系统畸形与心血管不稳定、胃肠功能障碍和神经母细胞瘤有关。更好地了解调节交感神经系统发育的因素对开发潜在的治疗方法至关重要。在这里，我们通过分析两种突变小鼠系：ISL1半胚系和神经嵴谱系中ISL1缺失的小鼠，发现了交感神经系统发育过程中LIM同源结构域转录因子ISL1的时间需求。在早期发育过程中，ISL1是交感神经元命运的决定、分化和胶质细胞分化的抑制所必需的，尽管它在初始的去甲肾上腺素能分化中是必不可少的。ISL1还通过调控细胞周期基因表达，在交感神经元增殖中发挥重要作用。在发育后期，通过维持去甲肾上腺素能分化而抑制胆碱能分化，ISL1是轴突生长和交感神经元多样化所必需的。对来自misl1突变体和对照胚胎的交感神经节的RNA-seq分析以及对交感神经节的ISL1 ChIP-seq分析表明，ISL1直接或间接地调节了几种不同的信号通路，这些信号通路协调了交感神经的发生。一些与神经母细胞瘤发病有关的基因是ISL1的直接下游靶点。我们的研究揭示了ISL1在交感神经元发育的多个方面的时间需求，并提示ISL1是神经母细胞瘤的候选基因。
Malformations of the sympathetic nervous system have been associated with cardiovascular instability, gastrointestinal dysfunction, and neuroblastoma. A better understanding of the factors regulating sympathetic nervous system development is critical to the development of potential therapies. Here, we have uncovered a temporal requirement for the LIM homeodomain transcription factor ISL1 during sympathetic nervous system development by the analysis of two mutant mouse lines: anIsl1hypomorphic line and mice withIsl1ablated in neural crest lineages. During early development, ISL1 is required for sympathetic neuronal fate determination, differentiation, and repression of glial differentiation, although it is dispensable for initial noradrenergic differentiation. ISL1 also plays an essential role in sympathetic neuron proliferation by controlling cell cycle gene expression. During later development, ISL1 is required for axon growth and sympathetic neuron diversification by maintaining noradrenergic differentiation, but repressing cholinergic differentiation. RNA-seq analyses of sympathetic ganglia fromIsl1mutant and control embryos, together with ISL1 ChIP-seq analysis on sympathetic ganglia, demonstrated that ISL1 regulates directly or indirectly several distinct signaling pathways that orchestrate sympathetic neurogenesis. A number of genes implicated in neuroblastoma pathogenesis are direct downstream targets of ISL1. Our study revealed a temporal requirement for ISL1 in multiple aspects of sympathetic neuron development, and suggestedIsl1as a candidate gene for neuroblastoma.
登录
查看更多内容
Isl1 是运动神经元发育多个方面所必需的
影响因子：
3.5
作者：
Liang, Xingqun;Song, Mi-Ryoung;Xu, ZengGuang;Lanuza, Guillermo M.;Liu, Yali;Zhuang, Tao;Chen, Yihan;Pfaff, Samuel L.;Evans, Sylvia M.;Sun, Yunfu
通讯作者：
Sun, Yunfu
影响因子：
5.3
作者：
Balamotis, Michael A.;Tamberg, Nele;Kohwi, Yoshinori
通讯作者：
Kohwi, Yoshinori
影响因子：
3.6
作者：
Becker, Juergen;Wang, Baigang;Wilting, Joerg
通讯作者：
Wilting, Joerg
DOI：
10.1158/1078-0432.ccr-08-0541
发表时间：
2008-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cheung IY;Feng Y;Gerald W;Cheung NK
通讯作者：
Cheung NK
DOI：
10.1126/science.1256271
发表时间：
2014-08-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lara-Astiaso D;Weiner A;Lorenzo-Vivas E;Zaretsky I;Jaitin DA;David E;Keren-Shaul H;Mildner A;Winter D;Jung S;Friedman N;Amit I
通讯作者：
Amit I