Richard-Parpaillon Laurent, Cosgrove Ruth A, Devine Christine, Vernon Ann E, Philpott Anna
Department of Oncology, Cambridge University, Hutchison/MRC Research Centre, Addenbrookes Hospital, Hills Road, Cambridge CB2 2XZ, UK.
Development. 2004 Jun;131(11):2577-86. doi: 10.1242/dev.01121. Epub 2004 Apr 28.
Cell division and differentiation are largely incompatible but the molecular links between the two processes are poorly understood. Here, we overexpress G1/S phase cyclins and cyclin-dependent kinases in Xenopus embryos to determine their effect on early development and differentiation. Overexpression of cyclin E prior to the midblastula transition (MBT), with or without cdk2, results in a loss of nuclear DNA and subsequent apoptosis at early gastrula stages. By contrast, overexpressed cyclin A2 protein does not affect early development and, when stabilised by binding to cdk2, persists to tailbud stages. Overexpression of cyclin A2/cdk2 in post-MBT embryos results in increased proliferation specifically in the epidermis with concomitant disruption of skin architecture and delay in differentiation. Moreover, ectopic cyclin A2/cdk2 also inhibits differentiation of primary neurons but does not affect muscle. Thus, overexpression of a single G1/S phase cyclin/cdk pair disrupts the balance between division and differentiation in the early vertebrate embryo in a tissue-specific manner.
细胞分裂和分化在很大程度上是不相容的，但这两个过程之间的分子联系却鲜为人知。在这里，我们在非洲爪蟾胚胎中过表达G1/S期细胞周期蛋白和细胞周期蛋白依赖性激酶，以确定它们对早期发育和分化的影响。在中囊胚转换（MBT）之前过表达细胞周期蛋白E，无论有无细胞周期蛋白依赖性激酶2（cdk2），都会导致早期原肠胚阶段核DNA的丢失和随后的细胞凋亡。相比之下，过表达的细胞周期蛋白A2蛋白不会影响早期发育，并且当通过与cdk2结合而稳定时，会持续到尾芽阶段。在MBT后的胚胎中过表达细胞周期蛋白A2/cdk2会导致特别是表皮的增殖增加，同时破坏皮肤结构并延迟分化。此外，异位表达的细胞周期蛋白A2/cdk2也会抑制原代神经元的分化，但不会影响肌肉。因此，过表达单个G1/S期细胞周期蛋白/细胞周期蛋白依赖性激酶对会以组织特异性方式破坏早期脊椎动物胚胎中分裂和分化之间的平衡。
