Mitotic cell rounding and epithelial thinning regulate lumen growth and shape

Mitotic cell rounding and epithelial thinning regulate lumen growth and shape
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DOI:
10.1038/ncomms8355
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发表时间:
2015-06-01
影响因子:
16.6
通讯作者:
Alsina, Berta
Alsina, Berta
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hoijman, Esteban;Rubbini, Davide;Alsina, Berta

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许多器官功能依赖于具有特定形状的上皮腔。这些空腔的形态发生异常可导致肾脏、大脑或内耳疾病。尽管它们具有相关性,但调节管腔尺寸的机制尚不清楚。在这里,我们对斑马鱼内耳发育进行实时成像,并在3D中定量分析管腔生长的动态。利用遗传、化学和机械干扰,我们确定了两种新的各向异性管腔生长的形态发生机制。第一种机制涉及上皮变薄,因为细胞改变形状并随着腔的扩张失去液体,提示器官内液体重新分配过程。激光显微外科实验揭示的第二种机制是,有丝分裂的圆形细胞在顶端基部收缩上皮,并机械地促进管腔的扩张。由于这些机制是轴特异性的,它们不仅调节管腔的生长,而且还调节腔的形状。
Many organ functions rely on epithelial cavities with particular shapes. Morphogenetic anomalies in these cavities lead to kidney, brain or inner ear diseases. Despite their relevance, the mechanisms regulating lumen dimensions are poorly understood. Here, we perform live imaging of zebrafish inner ear development and quantitatively analyse the dynamics of lumen growth in 3D. Using genetic, chemical and mechanical interferences, we identify two new morphogenetic mechanisms underlying anisotropic lumen growth. The first mechanism involves thinning of the epithelium as the cells change their shape and lose fluids in concert with expansion of the cavity, suggesting an intra-organ fluid redistribution process. In the second mechanism, revealed by laser microsurgery experiments, mitotic rounding cells apicobasally contract the epithelium and mechanically contribute to expansion of the lumen. Since these mechanisms are axis specific, they not only regulate lumen growth but also the shape of the cavity.