A regulatory gene network that directs micromere specification in the sea urchin embryo
A regulatory gene network that directs micromere specification in the sea urchin embryo
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DOI：
10.1006/dbio.2002.0627
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发表时间：
2002-06-01
影响因子：
2.7
通讯作者：
Davidson, EH
中科院分区：
文献类型：
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作者：
Oliveri, P;Carrick, DM;Davidson, EH
微粒及其直接后代在海胆的正常发育过程中具有三种已知的发育功能：在最初分离后，它们立即成为向相邻 veg(2) 细胞发出正常内中胚层规范所需的未识别信号的来源；几次裂解后，它们表达 Delta，这是一种 Notch 配体，可触发植物板中央中胚层结构域的条件规范；它们专门产生胃后胚胎的成骨间质。我们展示了解释微粒特异性的合子调控基因网络的关键组成部分。该网络是 Strongylocentrotus purpuratus 胚胎的整个内中胚层规范网络的一个子元素。一个新发现的编码配对类同源域转录因子的基因发挥着核心作用，该转录因子在微粒中充当阻遏物的阻遏物：该基因被命名为pmar1（配对类微粒抗阻遏物）。 pmar1 仅在卵裂和早期囊胚阶段表达，并且仅在微球中表达。一旦微团形成，它就会响应 Otx 和 beta-Catenin/Tcf 输入而被激活。 pmar1 基因产物介导的相互作用的抑制性质通过引入编码 Pmar1 因子的 mRNA 和编码 Engrailed-Pmar1 (En-Pmar1) 阻遏结构域融合的 mRNA 的相同效果来显示。在这两种情况下，效果都是去抑制： δ 基因；和成骨基因，包括通常仅在微米后代中表达的几种转录因子，以及一组下游成骨分化基因。携带编码Pmar1因子或En-Pmar1的外源mRNA的胚胎的空间表型是下游基因的表达域在大部分或全部胚胎上的扩展。这导致大部分胚胎转化为表达成骨标记的成骨间充质细胞。 pmar1 的正常作用是仅在微粒中阻止阻遏物的表达，而该阻遏物在整个胚胎中都起作用。该功能解释了 δ 转录在微米中的定位，从而解释了植物板中胚层的条件规范。它还解释了为什么骨骼分化基因组通常仅在微米后代中发挥作用。更一般地说，这项工作中出现的监管网络子元素表明，微粒功能的特异性如何取决于持续的全球监管相互作用以及早期的本地化输入。 (C) 2002 年爱思唯尔科学（美国）。
Micromeres and their immediate descendants have three known developmental functions in regularly developing sea urchins: immediately after their initial segregation, they are the source of an unidentified signal to the adjacent veg(2) cells that is required for normal endomesodermal specification; a few cleavages later, they express Delta, a Notch ligand which triggers the conditional specification of the central mesodermal domain of the vegetal plate; and they exclusively give rise to the skeletogenic mesenchyme of the postgastrular embryo. We demonstrate the key components of the zygotic regulatory gene network that accounts for micromere specificity. This network is a subelement of the overall endomesoderm specification network of the Strongylocentrotus purpuratus embryo. A central role is played by a newly discovered gene encoding a paired class homeodomain transcription factor which in micromeres acts as a repressor of a repressor: the gene is named pmar1 (paired-class micromere anti-repressor). pmar1 is expressed only during cleavage and early blastula stages, and exclusively in micromeres. It is initially activated as soon as the micromeres are formed, in response to Otx and beta-Catenin/Tcf inputs. The repressive nature of the interactions mediated by the pmar1 gene product was shown by the identical effect of introducing mRNA encoding the Pmar1 factor, and mRNA encoding an Engrailed-Pmar1 (En-Pmar1) repressor domain fusion. In both cases, the effects are derepression: of the delta gene; and of skeletogenic genes, including several transcription factors normally expressed only in micromere descendants, and also a set of downstream skeletogenic differentiation genes. The spatial phenotype of embryos bearing exogenous mRNA encoding Pmar1 factor or En-Pmar1 is expansion of the domains of expression of the downstream genes over most or all of the embryo. This results in transformation of much of the embryo into skeletogenic mesenchyme cells that express skeletogenic markers. The normal role of pmar1 is to prevent, exclusively in the micromeres, the expression of a repressor that is otherwise operative throughout the embryo. This function accounts for the localization of delta transcription in micromeres, and thereby for the conditional specification of the vegetal plate mesoderm. It also explains why skeletogenic differentiation gene batteries normally function only in micromere descendants. More generally, the regulatory network subelement emerging from this work shows how the specificity of micromere function depends on continuing global regulatory interactions, as well as on early localized inputs. (C) 2002 Elsevier Science (USA).