SoxB1 downregulation in vegetal lineages of sea urchin embryos is achieved by both transcriptional repression and selective protein turnover
SoxB1 downregulation in vegetal lineages of sea urchin embryos is achieved by both transcriptional repression and selective protein turnover
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DOI：
10.1242/dev.01650
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发表时间：
2005-03-01
期刊：
影响因子：
4.6
通讯作者：
Angerer, RC
中科院分区：
文献类型：
--
作者：
Angerer, LM;Newman, LA;Angerer, RC
细胞命运沿着海胆动物-植物胚胎轴的模式化需要核β-连环蛋白/TCF-Lef和SoxB1的相反功能，前者激活内中胚层基因调控网络，后者拮抗β-连环蛋白并限制其功能范围。这种相互作用的一个重要方面是SoxB1的时间控制下调，首先在micromeres，然后在macromere的后代。我们发现，SoxB1在这些谱系中的蛋白质周转水平受到调节。该机制依赖于核β-连环蛋白功能。它可以被Pmar 1激活，但不能被Krl激活，这两者都在β-连环蛋白/TCF-Lef的下游发挥作用。至少部分不同的，谱系特异性机制的运作，在大粒细胞的营业额取决于SoxB1进入细胞核，并在冗余的破坏信号，这两个都是不需要在micromeres。这些周转机制都不适用于产生外胚层的中节后代。然而，在mesomeres中，SoxB1似乎是受到负的自动调节，这有助于保持严格的调节SoxB1 mRNA水平在假定的外胚层。在第七和第十卵裂阶段之间，β-连环蛋白不仅促进SoxB1的降解，而且抑制其信息在大粒细胞衍生的卵裂球中的积累。总的来说，这些不同的机制可以精确地调节沿着动物-植物轴排列的不同层次的卵裂球后代中SoxB1的水平。
Patterning of cell fates along the sea urchin animal-vegetal embryonic axis requires the opposing functions of nuclear beta-catenin/TCF-Lef, which activates the endomesoderm gene regulatory network, and SoxB1, which antagonizes beta-catenin and limits its range of function. A crucial aspect of this interaction is the temporally controlled downregulation of SoxB1, first in micromeres and then in macromere progeny. We show that SoxB1 is regulated at the level of protein turnover in these lineages. This mechanism is dependent on nuclear P-catenin function. It can be activated by Pmar1, but not by Krl, both of which function downstream of beta-catenin/TCF-Lef. At least partially distinct, lineage-specific mechanisms operate, as turnover in the macromeres depends on entry of SoxB1 into nuclei, and on redundant destruction signals, neither of which is required in micromeres. Neither of these turnover mechanisms operates in mesomere progeny, which give rise to ectoderm. However, in mesomeres, SoxB1 appears to be subject to negative autoregulation that helps to maintain tight regulation of SoxB1 mRNA levels in presumptive ectoderm. Between the seventh and tenth cleavage stages, beta-catenin not only promotes degradation of SoxB1, but also suppresses accumulation of its message in macromere-derived blastomeres. Collectively, these different mechanisms work to regulate precisely the levels of SoxB1 in the progeny of different tiers of blastomeres arrayed along the animal-vegetal axis.