Yang Jing, Tan Change, Darken Rachel S, Wilson Paul A, Klein Peter S
Department of Medicine (Hematology-Oncology) and Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Development. 2002 Dec;129(24):5743-52. doi: 10.1242/dev.00150.
Following fertilization, the zygotic genome in many organisms is quiescent until the midblastula transition (MBT), when large-scale transcription begins. In Xenopus embryos, for example, transcription is believed to be repressed until the twelfth cell division. Thus, although dorsal-ventral patterning begins during the first cell cycle, little attention has been given to transcriptional regulation in pre-MBT development. We present evidence that regulated transcription begins during early cleavage stages and that the beta-catenin-Tcf complex is required for the transcription of the Xenopus nodal genes Xnr5 and Xnr6 as early as the 256-cell stage. Moreover, inhibition of beta-catenin/Tcf function can block dorsal development, but only if the inhibition begins early and is maintained throughout pre-MBT stages. Dorsal development can be rescued in ventralized embryos if Tcf-dependent transcription is activated prior to MBT, but activation of Tcf after MBT cannot rescue ventralized embryos, suggesting that beta-catenin/Tcf-dependent transcription is required prior to MBT for dorsal-ventral patterning in Xenopus.
受精后,许多生物体中的合子基因组处于静止状态,直到中囊胚转换(MBT)时大规模转录开始。例如,在非洲爪蟾胚胎中,转录被认为在第十二次细胞分裂之前受到抑制。因此,尽管背腹模式在第一个细胞周期就开始了,但对于MBT前发育过程中的转录调控却很少有人关注。我们提供的证据表明,在早期卵裂阶段就开始了受调控的转录,并且早在256细胞阶段,β-连环蛋白-Tcf复合物就参与非洲爪蟾节点基因Xnr5和Xnr6的转录。此外,抑制β-连环蛋白/Tcf功能会阻断背侧发育,但前提是抑制必须在早期开始并在整个MBT前阶段持续存在。如果在MBT之前激活Tcf依赖的转录,腹侧化胚胎中的背侧发育可以得到挽救,但在MBT之后激活Tcf则无法挽救腹侧化胚胎,这表明在非洲爪蟾中,背腹模式形成在MBT之前需要β-连环蛋白/Tcf依赖的转录。