Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein
Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein
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DOI：
10.1016/s0092-8674(00)81705-5
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发表时间：
1998-12-11
期刊：
影响因子：
64.5
通讯作者：
Hirokawa, N
中科院分区：
文献类型：
--
作者：
Nonaka, S;Tanaka, Y;Hirokawa, N
通过基因靶向破坏微管依赖性马达，小鼠KIF 3B。无效突变体没有生存超过妊娠中期，表现出生长迟缓，心包囊气球样变，神经管解体。显著的是，左右不对称是随机的心脏环路和胚胎转向的方向，lefty-2表达是双边或缺席。此外，节缺乏单纤毛，而基体存在。免疫细胞化学显示KIF 3B定位在野生型结纤毛。视频显微镜显示，这些纤毛是能动的，并产生一个螺旋流。这些数据表明，KIF 3 B是必不可少的左右决定通过纤毛内运输的材料纤毛发生的能动的初级纤毛，可以产生一个梯度的推定形态发生沿着左右轴的节点。
Microtubule-dependent motor, murine KIF3B, was disrupted by gene targeting. The null mutants did not survive beyond midgestation, exhibiting growth retardation, pericardial sac ballooning, and neural tube disorganization. Prominently, the left-right asymmetry was randomized in the heart loop and the direction of embryonic turning, lefty-2 expression was either bilateral or absent. Furthermore, the node lacked monocilia while the basal bodies were present. Immunocytochemistry revealed KIF3B localization in wildtype nodal cilia. Video microscopy showed that these cilia were motile and generated a leftward flow. These data suggest that KIF3B is essential for the left-right determination through intraciliary transportation of materials for ciliogenesis of motile primary cilia that could produce a gradient of putative morphogen along the left-right axis in the node.