Deficiency of mDia, an actin nucleator, disrupts integrity of neuroepithelium and causes periventricular dysplasia.
Deficiency of mDia, an actin nucleator, disrupts integrity of neuroepithelium and causes periventricular dysplasia.
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DOI：
10.1371/journal.pone.0025465
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Narumiya S
中科院分区：
文献类型：
--
作者：
Thumkeo D;Shinohara R;Watanabe K;Takebayashi H;Toyoda Y;Tohyama K;Ishizaki T;Furuyashiki T;Narumiya S
在中枢神经系统发育过程中，神经上皮细胞的顶基极性对神经干细胞增殖和分化的稳态至关重要。虽然在神经上皮细胞的顶端表面的adherens连接是重要的极性维持，这些adherens连接的完整性的分子机制调节仍然在很大程度上是未知的。鉴于肌动蛋白细胞骨架在粘附连接中的重要性，我们分析了mDia，肌动蛋白成核剂和Rho效应器，在顶端粘附连接的完整性中的作用。在这里，我们表明，mDia 1和mDia 3在发育中的大脑中表达，而mDia 3集中在神经上皮的顶端表面。缺乏mDia 1和mDia 3的小鼠在整个发育中的大脑中广泛发展脑室周围发育不良肿块，其中神经上皮细胞极性受损，顶端肌动蛋白带减弱，顶端粘附连接丧失。此外，电子显微镜分析显示，在其余地区的神经上皮细胞的异常收缩和顶膜隆起。此外，Rho的扰动，而不是ROCK的扰动，导致类似于mDia缺陷小鼠的顶端肌动蛋白带和粘附连接的丢失。这些结果表明，肌动蛋白细胞骨架调节Rho-mDia途径是至关重要的粘附连接的完整性和神经上皮细胞的极性，这一信号的损失诱导异常，异位增殖和分化的神经干细胞。
During development of the central nervous system, the apical-basal polarity of neuroepithelial cells is critical for homeostasis of proliferation and differentiation of neural stem cells. While adherens junctions at the apical surface of neuroepithelial cells are important for maintaining the polarity, the molecular mechanism regulating integrity of these adherens junctions remains largely unknown. Given the importance of actin cytoskeleton in adherens junctions, we have analyzed the role of mDia, an actin nucleator and a Rho effector, in the integrity of the apical adherens junction. Here we show that mDia1 and mDia3 are expressed in the developing brain, and that mDia3 is concentrated in the apical surface of neuroepithelium. Mice deficient in both mDia1 and mDia3 develop periventricular dysplastic mass widespread throughout the developing brain, where neuroepithelial cell polarity is impaired with attenuated apical actin belts and loss of apical adherens junctions. In addition, electron microscopic analysis revealed abnormal shrinkage and apical membrane bulging of neuroepithelial cells in the remaining areas. Furthermore, perturbation of Rho, but not that of ROCK, causes loss of the apical actin belt and adherens junctions similarly to mDia-deficient mice. These results suggest that actin cytoskeleton regulated by Rho-mDia pathway is critical for the integrity of the adherens junctions and the polarity of neuroepithelial cells, and that loss of this signaling induces aberrant, ectopic proliferation and differentiation of neural stem cells.
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影响因子：
16.2
作者：
Bultje, Ronald S.;Castaneda-Castellanos, David R.;Jan, Lily Yen;Jan, Yuh-Nung;Kriegstein, Arnold R.;Shi, Song-Hai
通讯作者：
Shi, Song-Hai
影响因子：
5.3
作者：
Herzog, Dominik;Loetscher, Pirmin;Relvas, Joao B.
通讯作者：
Relvas, Joao B.
影响因子：
13.9
作者：
Kriegstein A;Alvarez-Buylla A
通讯作者：
Alvarez-Buylla A
影响因子：
3.5
作者：
Narumiya, S;Ishizaki, T;Watanabe, N
通讯作者：
Watanabe, N
DOI：
10.1073/pnas.0603533103
发表时间：
2006-10-31
影响因子：
11.1
作者：
Chen, Lei;Liao, Guanghong;Zheng, Yi
通讯作者：
Zheng, Yi