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Title: Induction of Excess Centrosomes in Neural Progenitor Cells during the Development of Radiation-Induced Microcephaly
Authors: Shimada, Mikio
Matsuzaki, Fumio
Kato, Akihiro
Kobayashi, Junya  kyouindb  KAKEN_id
Matsumoto, Tomohiro  kyouindb  KAKEN_id
Komatsu, Kenshi
Author's alias: 小林, 純也
松本, 智裕
小松, 賢志
Issue Date: 1-Jul-2016
Publisher: Public Library of Science (PLoS)
Journal title: PLOS ONE
Volume: 11
Issue: 7
Thesis number: e0158236
Abstract: The embryonic brain is one of the tissues most vulnerable to ionizing radiation. In this study, we showed that ionizing radiation induces apoptosis in the neural progenitors of the mouse cerebral cortex, and that the surviving progenitor cells subsequently develop a considerable amount of supernumerary centrosomes. When mouse embryos at Day 13.5 were exposed to γ-rays, brains sizes were reduced markedly in a dose-dependent manner, and these size reductions persisted until birth. Immunostaining with caspase-3 antibodies showed that apoptosis occurred in 35% and 40% of neural progenitor cells at 4 h after exposure to 1 and 2 Gy, respectively, and this was accompanied by a disruption of the apical layer in which mitotic spindles were positioned in unirradiated mice. At 24 h after 1 Gy irradiation, the apoptotic cells were completely eliminated and proliferation was restored to a level similar to that of unirradiated cells, but numerous spindles were localized outside the apical layer. Similarly, abnormal cytokinesis, which included multipolar division and centrosome clustering, was observed in 19% and 24% of the surviving neural progenitor cells at 48 h after irradiation with 1 and 2 Gy, respectively. Because these cytokinesis aberrations derived from excess centrosomes result in growth delay and mitotic catastrophe-mediated cell elimination, our findings suggest that, in addition to apoptosis at an early stage of radiation exposure, radiation-induced centrosome overduplication could contribute to the depletion of neural progenitors and thereby lead to microcephaly.
Rights: © 2016 Shimada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
URI: http://hdl.handle.net/2433/227267
DOI(Published Version): 10.1371/journal.pone.0158236
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