Cell cycle-related genesp57kip2, Cdk5andSpinin the pathogenesis of neural tube defects*

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Abstract

Research Highlights

(1) Genes that were differentially expressed in normal embryos and embryos with developmental neural tube defects at embryonic days 9.5 and 10.5 were compared using gene chip analysis, providing the first functional classification of differentially-expressed genes in neural tube defects.

Research Highlights

(2) Genes related to apoptosis, signal transduction, transcription and translation regulation, protein synthesis and regulation, matrix and cytoskeletal proteins, energy and metabolism, and especially the cell cycle, were all involved in the pathogenesis of neural tube defects.

Research Highlights

(3) Cell cycle-related genes including p57kip2, Cdk5 and Spin were downregulated by retinoic acid, but upregulated in the normal neural tube.

Research Highlights

(4) This study provides the basis for further research into the mechanisms underlying developmental neural tube defects, and for the prenatal screening and diagnosis of these defects.

In the field of developmental neurobiology, accurate and ordered regulation of the cell cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified several genes involved in the development of neural tube defects. In this study, we established a model of developmental neural tube defects by administration of retinoic acid to pregnant rats. Gene chip hybridization analysis showed that genes related to the cell cycle and apoptosis, signal transduction, transcription and translation regulation, energy and metabolism, heat shock, and matrix and cytoskeletal proteins were all involved in the formation of developmental neural tube defects. Among these, cell cycle-related genes were predominant. Retinoic acid ment caused differential expression of three cell cycle-related genes p57kip2, Cdk5 and Spin, the expression levels of which were downregulated by retinoic acid and upregulated during normal neural tube formation. The results of this study indicate that cell cycle-related genes play an important role in the formation of neural tube defects. P57kip2, Cdk5 and Spin may be critical genes in the pathogenesis of neural tube defects.

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