In utero exposure to dioxin causes neocortical dysgenesis through the actions of p27Kip1

Takayuki Mitsuhashi, Junzo Yonemoto, Hideko Sone, Yasuhiro Kosuge, Kenjiro Kosaki, Takao Takahashi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 p27Kip1 in nuclei of neural progenitors. Lending support to this presumption, mice lacking p27Kip1 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 p27Kip1.

Original languageEnglish
Pages (from-to)16331-16335
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number37
DOIs
Publication statusPublished - 2010 Sep 14

Keywords

  • Cell cycle
  • Cerebral cortex
  • Development
  • Environmental pollutants
  • Neuronal progenitor cells

ASJC Scopus subject areas

  • General

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