title: Ionizing radiation downregulates ASPM, a gene responsible for microcephaly in humans.
abstract: Microcephaly is a malformation associated with in utero exposed atomic bomb survivors and can be induced in mice by fetal exposure to ionizing radiation (IR). The pathogenesis of IR-induced microcephaly, however, has not been fully understood. Our analyses of high-coverage expression profiling (HiCEP) demonstrated that the abnormal spindle-like microcephaly associated gene (ASPM) was down-regulated in irradiated human diploid fibroblasts. ASPM was recently reported as the causative gene for MCPH-5, the most common type of congenital microcephaly in humans. Here, we show that the expression of the Aspm gene was significantly reduced by IR in various human and murine cells. Additionally, Aspm was found downregulated in the irradiated fetal mouse brain, particularly in the ventricular zones. A similar suppression was observed in the irradiated neurosphere cultures. This is the first report suggesting that the suppression of Aspm by IR could be the initial molecular target leading to the future microcephaly formation.
authors.affiliation: Cellular and Molecular Biology Team, National Institute of Radiological Sciences, Heavy-Ion Radiobiology Research Group, Research Center for Charged Particle Therapy, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fujimori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yaoi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogi
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Suetomi
authors.forename: Emiko
authors.initials: E
authors.lastname: Sekine
authors.forename: Dong
authors.initials: D
authors.lastname: Yu
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Kato
authors.forename: Sentaro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Okayasu
authors.forename: Kyoko
authors.initials: K
authors.lastname: Itoh
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000528:radiation effects*; D002460:Cell Line; D015536:Down-Regulation; D015870:Gene Expression / Q000528:radiation effects*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008831:Microcephaly / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000235:genetics*; D011859:Radiography; D013234:Stem Cells / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: C467202:ASPM protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger