Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 37, Pages 16331-16335Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1002960107
Keywords
environmental pollutants; cerebral cortex; development; neuronal progenitor cells; cell cycle
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [17790723, 20790744, 22791001]
- Japan Society for the Promotion of Science (JSPS) [15390327, 18390302, 20390299]
- Grants-in-Aid for Scientific Research [20390299, 17790723, 20790744, 18390302, 22791001, 15390327] Funding Source: KAKEN
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Dioxins have been reported to exert various adverse effects, including cell-cycle dysregulation in vitro and impairment of spatial learning and memory after in utero exposure in rodents. Furthermore, children born to mothers who are exposed to dioxin analogs polychlorinated dibenzofurans or polychlorinated biphenyls have developmental impairments in cognitive functions. Here, we show that in utero exposure to dioxins in mice alters differentiation patterns of neural progenitors and leads to decreased numbers of non-GABAergic neurons and thinner deep neocortical layers. This reduction in number of non-GABAergic neurons is assumed to be caused by accumulation of cyclin-dependent kinase inhibitor p27(Kip1) in nuclei of neural progenitors. Lending support to this presumption, mice lacking p27(Kip1) are not susceptible to in utero dioxin exposure. These results show that environmental pollutants may affect neocortical histogenesis through alterations of functions of specific gene(s)/protein(s) (in our case, dioxins), exerting adverse effects by altering functions of p27(Kip1).
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