Spatially dependent dynamic MAPK modulation by the Nde1-Lis1-Brap complex patterns mammalian CNS.
Spatially dependent dynamic MAPK modulation by the Nde1-Lis1-Brap complex patterns mammalian CNS.
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DOI：
10.1016/j.devcel.2013.04.006
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发表时间：
2013-05-13
影响因子：
11.8
通讯作者：
Feng, Yuanyi
中科院分区：
文献类型：
--
作者：
Lanctot, Alison A.;Peng, Chian-Yu;Pawlisz, Ashley S.;Joksimovic, Milan;Feng, Yuanyi
在中枢神经系统发育中调节细胞增殖和分化需要非常复杂和精确。神经祖细胞从中线信号中心接收分级重叠信号，但每个神经祖细胞都以时空限制的模式做出独特的细胞命运决定。Nde 1-Lis 1复合物根据相对于中线的地理位置调节个体化细胞命运决定。虽然远离中线的细胞在Nde 1-Lis 1双突变CNS中不能自我更新，但嵌入信号中心的细胞显示出明显的过度增殖。Lis 1和Brap（MAPK信号阈值调节剂）之间的直接相互作用介导了这种对促有丝分裂信号梯度的差异反应。Nde 1-Lis 1缺陷导致MAPK支架Ksr的空间依赖性改变和MAPK的过度激活。上位性分析支持协同BRAP和Lis 1功能。这些结果表明，Nde 1，Lis 1和Brap组成的分子复合物调节动态MAPK信号转导阈值在空间依赖性的方式。
Regulating cell proliferation and differentiation in CNS development requires both extraordinary complexity and precision. Neural progenitors receive graded overlapping signals from midline signaling centers, yet each makes a unique cell fate decision in a spatiotemporally restricted pattern. The Nde1-Lis1 complex regulates individualized cell fate decisions based on the geographical location with respect to the midline. While cells distant from the midline fail to self-renew in the Nde1-Lis1 double mutant CNS, cells embedded in the signaling centers showed marked over-proliferation. A direct interaction between Lis1 and Brap, a MAPK signaling threshold modulator, mediates this differential response to mitogenic signal gradients. Nde1-Lis1 deficiency resulted in a spatially-dependent alteration of MAPK scaffold Ksr and hyper-activation of MAPK. Epistasis analyses supported synergistic Brap and Lis1 functions. These results suggest that a molecular complex composed of Nde1, Lis1, and Brap regulates the dynamic MAPK signaling threshold in a spatially-dependent fashion.
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影响因子：
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