Ectodermal Factor Restricts Mesoderm Differentiation by Inhibiting p53
Ectodermal Factor Restricts Mesoderm Differentiation by Inhibiting p53
复制标题
DOI：
10.1016/j.cell.2008.03.035
复制
发表时间：
2008-05
期刊：
影响因子：
64.5
通讯作者：
Noriaki Sasai;Rieko Yakura;Daisuke Kamiya;Yoko Nakazawa;Y. Sasai
中科院分区：
文献类型：
--
作者：
Noriaki Sasai;Rieko Yakura;Daisuke Kamiya;Yoko Nakazawa;Y. Sasai
在两栖动物胚胎的原肠胚形成过程中，三个胚层（内胚层、外胚层和中胚层）的发育受母体和合子机制的调控。尽管已知中胚层特化需要TGF-β信号传导和p53活性之间的合作并且需要母体因子，但必需的合子因子一直难以捉摸。在此，我们报道了锌指蛋白XFDL 156是一种抑制中胚层分化的外胚层合子因子，XFDL 156过表达抑制中胚层标记物，其缺失诱导假定外胚层中胚层分化异常。此外，我们发现XFDL 156及其哺乳动物同源物与p53的C-末端调控区相互作用，从而抑制p53靶基因诱导和中胚层分化。因此，XFDL 156通过控制对p53的时空响应性来主动限制假定外胚层中的中胚层分化。
During gastrulation of the amphibian embryo, specification of the three germ layers, endo-, ecto-, and mesoderm, is regulated by maternal and zygotic mechanisms. Although it is known that mesoderm specification requires the cooperation between TGF-β signaling and p53 activity and requires maternal factors, essential zygotic factors have been elusive. Here, we report that the Zn-finger protein XFDL156 is an ectodermal, zygotic factor that suppresses mesodermal differentiation.XFDL156overexpression suppresses mesodermal markers, and its depletion induces aberrant mesodermal differentiation in the presumptive ectoderm. Furthermore, we find that XFDL156 and its mammalian homologs interact with the C-terminal regulatory region of p53, thereby inhibiting p53 target gene induction and mesodermal differentiation. Thus, XFDL156 actively restricts mesodermal differentiation in the presumptive ectoderm by controlling the spatiotemporal responsiveness to p53.