The polarity protein Pard3 is required for centrosome positioning during neurulation.

The polarity protein Pard3 is required for centrosome positioning during neurulation.
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DOI:
10.1016/j.ydbio.2010.01.034
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发表时间:
2010-05-15
影响因子:
2.7
通讯作者:
Brewster, Rachel
Brewster, Rachel
中科院分区:
生物学3区
文献类型:
--
作者:
Hong, Elim;Jayachandran, Pradeepa;Brewster, Rachel

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微管是细胞极性、构型和运动的重要调节因子。微管网络的组织是特定于上下文的。在非极化细胞中,微管固定在中心体上,形成放射状阵列。在大多数上皮细胞中,微管是非中心体的,沿着顶基轴排列,中心体模板为纤毛。因此,经历间充质向上皮间充质转变的细胞必须广泛重组其微管网络,但对这一过程是如何协调的却知之甚少。特别是,调节中心体顶端位置的途径尚不清楚,鉴于纤毛在流体推进、感觉和信号中的作用,这是一个中心问题。在斑马鱼中,神经前体细胞在神经形成过程中经历逐渐的上皮化,从而提供了一个方便的体内细胞环境来解决这个问题。在这里,我们证明了在神经形成过程中,微管细胞骨架逐渐从放射状组织转变为线状组织,微管与极性蛋白PARD3一起发挥作用,介导中心体的定位。PARD3耗尽会导致脑积水,这是一种经常与异常脑脊液流动相关的缺陷,与纤毛缺陷有关。因此,这些发现使发生在神经形成过程中的细胞事件成为焦点,并揭示了与中心体定位有关的新的分子机制。
Microtubules are essential regulators of cell polarity, architecture and motility. The organization of the microtubule network is context-specific. In non-polarized cells, microtubules are anchored to the centrosome and form radial arrays. In most epithelial cells, microtubules are noncentrosomal, align along the apico-basal axis and the centrosome templates a cilium. It follows that cells undergoing mesenchyme-to-epithelium transitions must reorganize their microtubule network extensively, yet little is understood about how this process is orchestrated. In particular, the pathways regulating the apical positioning of the centrosome are unknown, a central question given the role of cilia in fluid propulsion, sensation and signaling. In zebrafish, neural progenitors undergo progressive epithelialization during neurulation, and thus provide a convenient in vivo cellular context in which to address this question. We demonstrate here that the microtubule cytoskeleton gradually transitions from a radial to linear organization during neurulation and that microtubules function in conjunction with the polarity protein Pard3 to mediate centrosome positioning. Pard3 depletion results in hydrocephalus, a defect often associated with abnormal cerebrospinal fluid flow that has been linked to cilia defects. These findings thus bring to focus cellular events occurring during neurulation and reveal novel molecular mechanisms implicated in centrosome positioning.
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