Luo Huijun, Liu Xuesong, Wang Fang, Huang Qiuhua, Shen Shuhong, Wang Long, Xu Guojiang, Sun Xia, Kong Hui, Gu Mingmin, Chen Saijuan, Chen Zhu, Wang Zhugang
Laboratory of Genetic Engineering, Department of Medical Genetics, Institute of Health Science, Shanghai Second Medical University, 280 South Chong-qing Road, Shanghai 200025, PR China.
Mol Cell Neurosci. 2005 Aug;29(4):507-15. doi: 10.1016/j.mcn.2004.12.002.
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 E15.5 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 E 9.5 and E10.5 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(-/-) murine embryonic fibroblast 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.
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组织和神经系统发育。在此，我们表明，palladin的失活会导致胚胎致死，原因是颅神经管闭合严重缺陷以及肝脏和肠道疝出。研究发现，palladin(-/-)胚胎在E15.5左右死亡，并出现100%发生率的颅神经管闭合缺陷（NTDs）。全胚胎原位杂交显示，palladin在野生型早期胚胎（E8.5）中的表达特异性地局限于颅神经管褶皱隆起处，此处是神经管闭合开始的地方。Palladin的表达与在palladin(-/-)突变体中观察到的表型缺陷密切相关。而在E9.5和E10.5胚胎中，palladin广泛表达。体外研究表明，在palladin(-/-)小鼠胚胎成纤维细胞（MEFs）中，细胞质中应力纤维的形成、细胞对细胞外基质蛋白纤连蛋白的黏附能力以及细胞迁移都受到显著干扰。我们的研究结果表明，palladin在肌动蛋白应力纤维形成、细胞黏附和迁移中起重要作用。我们提出，palladin是神经管闭合起始所必需的，并且是一个可能与人类NTDs病因有关的重要新候选因素。
