Centriole Amplification in Zebrafish Affects Proliferation and Survival but Not Differentiation of Neural Progenitor Cells
Centriole Amplification in Zebrafish Affects Proliferation and Survival but Not Differentiation of Neural Progenitor Cells
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DOI：
10.1016/j.celrep.2015.08.062
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发表时间：
2015-10-06
期刊：
影响因子：
8.8
通讯作者：
Norden, Caren
中科院分区：
文献类型：
--
作者：
Dzafic, Edo;Strzyz, Paulina J.;Norden, Caren
在动物细胞中，由中心粒扩增引起的多余中心体引起有丝分裂畸变，并与包括小头畸形和癌症在内的疾病有关。为了评估中心粒扩增如何在细胞和组织水平上影响生物体发育，我们使用了斑马鱼的体内成像潜力。我们证明，中心粒扩增可以诱导多极后期，导致双核细胞。这种双核化引起神经上皮细胞的大量凋亡。有趣的是，并非所有上皮细胞对双核化都同样敏感，因为皮肤细胞耐受双核化而不进入凋亡。然而，在神经上皮中，双核导致组织变性和随后的生物体死亡。值得注意的是，这种组织变性可以通过野生型细胞的补偿性增殖来有效地抵消。由于产生双核子代的风险在每次细胞分裂时复发，因此神经上皮中的中心粒扩增在祖细胞增殖期间尤其有害。然而，一旦细胞达到分化阶段，中心粒扩增不会损害神经元分化。
In animal cells, supernumerary centrosomes, resulting from centriole amplification, cause mitotic aberrations and have been associated with diseases, including microcephaly and cancer. To evaluate how centriole amplification impacts organismal development at the cellular and tissue levels, we used the in vivo imaging potential of the zebrafish. We demonstrate that centriole amplification can induce multipolar anaphase, resulting in binucleated cells. Such binucleation causes substantial apoptosis in the neuroepithelium. Interestingly, not all epithelia are similarly sensitive to binucleation, as skin cells tolerate it without entering apoptosis. In the neuroepithelium, however, binucleation leads to tissue degeneration and subsequent organismal death. Notably, this tissue degeneration can be efficiently counterbalanced by compensatory proliferation of wild-type cells. Because the risk for generating a binucleated daughter recurs at every cell division, centriole amplification in the neuroepithelium is especially deleterious during progenitor proliferation. Once cells reach the differentiation phase, however, centriole amplification does not impair neuronal differentiation.