Disruption of palladin results in neural tube closure defects in mice
Disruption of palladin results in neural tube closure defects in mice
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DOI：
10.1016/j.mcn.2004.12.002
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发表时间：
2005-08-01
影响因子：
3.5
通讯作者：
Wang, ZG
中科院分区：
文献类型：
--
作者：
Luo, HJ;Liu, XS;Wang, ZG
Palladin是一种新发现的肌动蛋白相关蛋白，被认为参与肌动蛋白细胞骨架的组装和神经系统的发育。在这里，我们表明，失活的palladin导致胚胎死亡，由于严重缺陷的颅神经管关闭和疝的肝脏和肠道。结果发现palladin（-/-）胚胎在EI 5.5左右死亡，并发生颅神经管闭合缺陷（NTDs），其存活率为100%。全胚原位杂交显示，palladin在早期野生型胚胎（E8.5）的表达是特别限制在提升颅神经褶皱的神经管关闭启动。Palladin表达密切反映了在Palladin（-/-）突变体中观察到的表型缺陷。而在E9.5和E10.5胚中，palladin广泛表达。体外研究表明，palladin（-/-）海洋胚胎成纤维细胞（MEFs）细胞质中应力纤维的形成、细胞与细胞外基质蛋白纤维连接蛋白（FN）的粘附能力以及细胞迁移能力均受到显著影响。我们的研究结果表明，palladin在肌动蛋白应力纤维的形成，细胞粘附和迁移中发挥重要作用。我们认为palladin是神经管闭合启动所必需的，并提供了一个重要的新的候选人，可能涉及人类NTDs的病因。(c)2004年爱思唯尔公司All rights reserved.
Palladin is a newly identified actin-associated protein which was proposed to be involved in actin cytoskeleton organization and nervous system development. Here, we show that inactivation of palladin leads to embryonic lethality due to severe defects of cranial neural tube closure and herniation of liver and intestine. It was found that palladin(-/-) embryos died around EI5.5 and developed cranial neural tube closure defects (NTDs) with 100% penetrance. Whole mount in situ hybridization revealed that expression of palladin in early wild type embryos (E8.5) was specifically restricted in the elevating cranial neural folds where the neural tube closure is initiated. Palladin expression closely mirrors the phenotypic defects observed in palladin(-/-) mutants. While in E9.5 and El 0.5 embryos palladin was ubiquitously expressed. In vitro study revealed that formation of stress fibers in cytoplasm, cell adherent ability to extra-cellular matrix protein fibronectin and cell migration were dramatically disturbed in palladin(-/-) marine embryonic flbroblast cells (MEFs). Our findings suggest that palladin plays important roles in actin stress fiber formation, cell adhesion and migration. We propose that palladin is required for the initiation of neural tube closure and provides an important new candidate that may be implicated in the etiology of human NTDs. (c) 2004 Elsevier Inc. All rights reserved.