A critical role of Pax6 in alcohol-induced fetal microcephaly

Ying Peng; Pai-Hao Yang; Samuel S.M Ng; Oscar G Wong; Jie Liu; Ming-Liang He; Hsiang-Fu Kung; Marie C.M Lin

Neurobiology of Disease (Jul 2004)

A critical role of Pax6 in alcohol-induced fetal microcephaly

Ying Peng,
Pai-Hao Yang,
Samuel S.M Ng,
Oscar G Wong,
Jie Liu,
Ming-Liang He,
Hsiang-Fu Kung,
Marie C.M Lin

Affiliations

Ying Peng: Institute 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, China
Pai-Hao Yang: Institute 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, China
Samuel S.M Ng: Institute 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, China
Oscar G Wong: Institute 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, China
Jie Liu: Institute 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, China
Ming-Liang He: Institute 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, China
Hsiang-Fu Kung: Institute 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, China
Marie C.M Lin: Institute 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, China

Journal volume & issue: Vol. 16, no. 2
pp. 370 – 376

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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