A critical role of Pax6 in alcohol-induced fetal microcephaly
Maternal alcohol abuse during pregnancy is one of the leading causes of birth defects in humans. Despite extensive studies, the molecular basis is still not clear. Here we transiently exposed Xenopus embryos to alcohol and showed that alcohol dose-dependently produced microcephaly and growth retarda...
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doaj-3dec6399bb5b4f9b9880dec3c43830fd2021-03-20T04:49:37ZengElsevierNeurobiology of Disease1095-953X2004-07-01162370376A critical role of Pax6 in alcohol-induced fetal microcephalyYing Peng0Pai-Hao Yang1Samuel S.M Ng2Oscar G Wong3Jie Liu4Ming-Liang He5Hsiang-Fu Kung6Marie C.M Lin7Institute of Molecular Biology and Open Lab of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong, China; Department of Neurology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, ChinaInstitute of Molecular Biology and Open Lab of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong, China; Department of Neurology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, ChinaInstitute of Molecular Biology and Open Lab of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong, China; Department of Neurology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, ChinaInstitute of Molecular Biology and Open Lab of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong, China; Department of Neurology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, ChinaInstitute of Molecular Biology and Open Lab of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong, China; Department of Neurology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, ChinaInstitute of Molecular Biology and Open Lab of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong, China; Department of Neurology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, ChinaInstitute of Molecular Biology and Open Lab of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong, China; Department of Neurology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, ChinaInstitute of Molecular Biology and Open Lab of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong, China; Department of Neurology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, ChinaMaternal alcohol abuse during pregnancy is one of the leading causes of birth defects in humans. Despite extensive studies, the molecular basis is still not clear. Here we transiently exposed Xenopus embryos to alcohol and showed that alcohol dose-dependently produced microcephaly and growth retardation. Moreover, it reduced the expression of several key neural genes (xPax6, xOtx2, xSox3, xSox2, and xNCAM), of which xPax6 was most vulnerable. An alcohol concentration as low as 0.3% could produce more than 90% reduction of xPax6 expression. Consistently, microinjection of xPax6 expression plasmid to Xenopus embryos dose-dependently rescued alcohol-induced microcephaly and restored the expression of xOtx2, xSox3, xSox2, and xNCAM. To test whether reactive oxygen species (ROS) is the upstream signal for alcohol-induced microcephaly and xPax6 suppression, we overexpressed catalase in Xenopus embryos and found that catalase not only decreased alcohol-induced H2O2 formation, but also fully restored Pax6 expression and reversed microcephaly. In contrast, xPax6 and catalase could only provide partial protection against growth retardation. Results from this study illustrate for the first time the critical role of H2O2-mediated Pax6 suppression in alcohol-induced microcephaly and suggest the presence of additional mechanisms for alcohol-induced fetal growth retardation.http://www.sciencedirect.com/science/article/pii/S0969996104000622Fetal alcohol syndromeMicrocephalyPax6Reactive oxygen species |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ying Peng Pai-Hao Yang Samuel S.M Ng Oscar G Wong Jie Liu Ming-Liang He Hsiang-Fu Kung Marie C.M Lin |
spellingShingle |
Ying Peng Pai-Hao Yang Samuel S.M Ng Oscar G Wong Jie Liu Ming-Liang He Hsiang-Fu Kung Marie C.M Lin A critical role of Pax6 in alcohol-induced fetal microcephaly Neurobiology of Disease Fetal alcohol syndrome Microcephaly Pax6 Reactive oxygen species |
author_facet |
Ying Peng Pai-Hao Yang Samuel S.M Ng Oscar G Wong Jie Liu Ming-Liang He Hsiang-Fu Kung Marie C.M Lin |
author_sort |
Ying Peng |
title |
A critical role of Pax6 in alcohol-induced fetal microcephaly |
title_short |
A critical role of Pax6 in alcohol-induced fetal microcephaly |
title_full |
A critical role of Pax6 in alcohol-induced fetal microcephaly |
title_fullStr |
A critical role of Pax6 in alcohol-induced fetal microcephaly |
title_full_unstemmed |
A critical role of Pax6 in alcohol-induced fetal microcephaly |
title_sort |
critical role of pax6 in alcohol-induced fetal microcephaly |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2004-07-01 |
description |
Maternal alcohol abuse during pregnancy is one of the leading causes of birth defects in humans. Despite extensive studies, the molecular basis is still not clear. Here we transiently exposed Xenopus embryos to alcohol and showed that alcohol dose-dependently produced microcephaly and growth retardation. Moreover, it reduced the expression of several key neural genes (xPax6, xOtx2, xSox3, xSox2, and xNCAM), of which xPax6 was most vulnerable. An alcohol concentration as low as 0.3% could produce more than 90% reduction of xPax6 expression. Consistently, microinjection of xPax6 expression plasmid to Xenopus embryos dose-dependently rescued alcohol-induced microcephaly and restored the expression of xOtx2, xSox3, xSox2, and xNCAM. To test whether reactive oxygen species (ROS) is the upstream signal for alcohol-induced microcephaly and xPax6 suppression, we overexpressed catalase in Xenopus embryos and found that catalase not only decreased alcohol-induced H2O2 formation, but also fully restored Pax6 expression and reversed microcephaly. In contrast, xPax6 and catalase could only provide partial protection against growth retardation. Results from this study illustrate for the first time the critical role of H2O2-mediated Pax6 suppression in alcohol-induced microcephaly and suggest the presence of additional mechanisms for alcohol-induced fetal growth retardation. |
topic |
Fetal alcohol syndrome Microcephaly Pax6 Reactive oxygen species |
url |
http://www.sciencedirect.com/science/article/pii/S0969996104000622 |
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