{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T12:07:08Z","timestamp":1772885228681,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,6,10]],"date-time":"2010-06-10T00:00:00Z","timestamp":1276128000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> Prenatal exposure to methylnitrosourea (MNU), an alkylating agent, induces microcephaly in mice. However, its pathogenetic mechanism has not been clarified, especially that in the development of the cerebral cortex. <jats:bold>METHODS:<\/jats:bold> ICR mice were treated with MNU at 10\u2009mg\/kg intraperitoneally on day 13.5 or 15.5 of gestation, and the embryos were observed histologically 24\u2009hr after treatment with MNU or at term. To clarify the pathogenesis of microcephaly and histological changes, especially apoptosis, neurogenesis, and neural migration\/positioning, we performed histological analysis employing a cell\u2010specific labeling experiment using thymidine\u2010like substances (BrdU, CldU, and IdU) and markers of neurons\/neural stem cells. <jats:bold>RESULTS:<\/jats:bold> Histological abnormalities of the dorsal telencephalon, and the excessive cell death of proliferative neural progenitor\/stem cells were noted in the MNU\u2010treated embryos. The highest frequencies of cell death occurred at 36\u2009hr after MNU treatment, and little or no neurogenesis was observed in the ventricular zone of the dorsal telencephalon. Abnormality of the radial migration was caused by the reduction of radial fibers in the radial glias. Birth\u2010date analysis revealed the abnormal positioning of neurons and aberrant lamination of the cerebral cortex. <jats:bold>CONCLUSIONS:<\/jats:bold> Our data suggest that prenatal exposure to MNU induces the excessive cell death of neural precursor\/stem cells, and the defective development of the cerebral cortex, resulting in microcephalic abnormalities. <jats:italic>Birth Defects Res (Part B)<\/jats:italic> 89:213\u2013222, 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.20245","type":"journal-article","created":{"date-parts":[[2010,6,10]],"date-time":"2010-06-10T18:47:05Z","timestamp":1276195625000},"page":"213-222","source":"Crossref","is-referenced-by-count":17,"title":["Methylnitrosourea induces neural progenitor cell apoptosis and microcephaly in mouse 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