Journal of Biological Chemistry
Volume 281, Issue 52, 29 December 2006, Pages 40440-40449
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Molecular Basis of Cell and Developmental Biology
YB-1 Is Important for an Early Stage Embryonic Development: NEURAL TUBE FORMATION AND CELL PROLIFERATION*

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The eukaryotic Y-box-binding protein-1 (YB-1) is involved in the transcriptional and translational control of many biological processes, including cell proliferation. In clinical studies, the cellular level of YB-1 closely correlates with tumor growth and prognosis. To understand the role of YB-1 in vivo, especially in the developmental process, we generated YB-1 knock-out mice, which are embryonic lethal and exhibit exencephaly associated with abnormal patterns of cell proliferation within the neuroepithelium. β-Actin expression and F-actin formation were reduced in the YB-1 null embryo and YB-1-/- mouse embryonic fibroblasts, suggesting that the neural tube defect is caused by abnormal cell morphology and actin assembly within the neuroepithelium. Fibroblasts derived from YB-1-/- embryos demonstrated reduced growth and cell density. A colony formation assay showed that YB-1-/- mouse embryonic fibroblasts failed to undergo morphological transformation and remained contact-inhibited in culture. These results demonstrate that YB-1 is involved in early mouse development, including neural tube closure and cell proliferation.

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This work was supported by a grant-in-aid for scientific research on the priority area of ABC proteins, Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Corp. (JST), the second-term comprehensive 10-year strategy for cancer control from the Ministry of Health and Welfare of Japan, and the Cancer Research fund from Ministry of Education, Culture, Sports, Science, and Technology, Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Experimental Procedures and Figs. S1 and S2.