Hippi is essential for node cilia assembly and Sonic hedgehog signaling
Hippi is essential for node cilia assembly and Sonic hedgehog signaling
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DOI：
10.1016/j.ydbio.2006.09.001
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发表时间：
2006-12-15
影响因子：
2.7
通讯作者：
Nicholson, Donald W.
中科院分区：
文献类型：
--
作者：
Houde, Caroline;Dickinson, Robin J.;Nicholson, Donald W.
Hippi作为一种适配器蛋白，介导从多谷氨酰胺扩展的亨廷顿蛋白（一种亨廷顿病的确定原因）到外源性细胞死亡途径的促凋亡信号。为了探索Hippi的其他功能，我们产生了Hippi敲除小鼠。这种缺失导致胚胎转动过程和心脏循环的随机化，这是左-右（LR）轴模式缺陷的标志。我们报道，通常存在于胚胎结表面的可运动单纤毛在Hippi（-/-）胚胎中不存在，并提出了启动LR对称的断裂。此外，还观察到中枢神经系统发育的缺陷。在Hippi缺失的情况下，神经管中的Sonic hedgehog （Shh）通路下调，导致腹侧神经细胞命运无法建立。综上所述，这些发现表明Hippi在发育过程中在纤毛组装和Shh信号传导中具有双重作用，此外它还在成年大脑在病理性应激条件下的凋亡信号转导中发挥作用。(c) 2006爱思唯尔公司版权所有。
Hippi functions as an adapter protein that mediates pro-apoptotic signaling from poly-glutamine-expanded huntingtin, an established cause of Huntington disease, to the extrinsic cell death pathway. To explore other functions of Hippi we generated Hippi knock-out mice. This deletion causes randomization of the embryo turning process and heart looping, which are hallmarks of defective left-right (LR) axis patterning. We report that motile monocilia normally present at the surface of the embryonic node, and proposed to initiate the break in LR symmetry, are absent on Hippi(-/-) embryos. Furthermore, defects in central nervous system development are observed. The Sonic hedgehog (Shh) pathway is downregulated in the neural tube in the absence of Hippi, which results in failure to establish ventral neural cell fate. Together, these findings demonstrate a dual role for Hippi in cilia assembly and Shh signaling during development, in addition to its proposed role in apoptosis signal transduction in the adult brain under pathogenically stressful conditions. (c) 2006 Elsevier Inc. All rights reserved.