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

First Author  Mitsuhashi T Year  2010
Journal  Proc Natl Acad Sci U S A Volume  107
Issue  37 Pages  16331-5
PubMed ID  20805476 Mgi Jnum  J:164371
Mgi Id  MGI:4833730 Doi  10.1073/pnas.1002960107
Citation  Mitsuhashi T, et al. (2010) In utero exposure to dioxin causes neocortical dysgenesis through the actions of p27Kip1. Proc Natl Acad Sci U S A 107(37):16331-5
abstractText  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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