Cyclin D and cdk4 are required for normal development beyond the blastula stage in sea urchin embryos
Cyclin D and cdk4 are required for normal development beyond the blastula stage in sea urchin embryos
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DOI：
10.1128/mcb.22.13.4863-4875.2002
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发表时间：
2002-07-01
影响因子：
5.3
通讯作者：
Marzluff, WF
中科院分区：
文献类型：
--
作者：
Moore, JC;Sumerel, JL;Marzluff, WF
CDK4mRNA和蛋白在海胆卵和整个胚胎发育过程中都有结构性表达。相反，当细胞周期由交替的S和M期组成时，在卵子和早期胚胎中几乎检测不到细胞周期蛋白D基因。细胞周期蛋白D在胚泡早期显著增加，并在整个胚胎发育过程中保持恒定水平。CDK4激酶活性的增加伴随着细胞周期蛋白D基因表达的增加。Cyclin D在卵子中的异位表达阻碍了16-细胞期之前的发育，并最终导致胚胎死亡，这表明卵裂细胞周期中Cyclin D/CDK4的激活对胚胎是致命的。相反，用吗啉反义寡核苷酸阻断细胞周期蛋白D或CDK4的表达会导致原肠胚期早期胚胎的正常发育，但会导致异常的、不对称的幼虫。这些结果表明，在海胆中，细胞周期蛋白D和CDK4是正常发育所必需的，也可能是发育中的胚胎形成模式所必需的，但可能不直接参与调节进入细胞周期。
cdk4 mRNA and protein are constitutively expressed in sea urchin eggs and throughout embryonic development. In contrast, cyclin D mRNA is barely detectable in eggs and early embryos, when the cell cycles consist of alternating S and M phases. Cyclin D mRNA increases dramatically in embryos at the early blastula stage and remains at a constant level throughout embryogenesis. An increase in cdk4 kinase activity occurs concomitantly, with the increase in cyclin D mRNA. Ectopic expression of cyclin D mRNA in eggs arrests development before the 16-cell stage and causes eventual embryonic death, suggesting that activation of cyclin D/cdk4 in cleavage cell cycles is lethal to the embryo. In contrast, blocking cyclin D or cdk4 expression with morpholino antisense oligonucleotides results in normal development of early gastrula-stage embryos but abnormal, asymmetric larvae. These results suggest that in sea urchins, cyclin D and cdk4 are required for normal development and perhaps the patterning of the developing embryo, but may not be directly involved in regulating entry into the cell cycle.