Anteroposterior axis patterning by early canonical Wnt signaling during hemichordate development.

Anteroposterior axis patterning by early canonical Wnt signaling during hemichordate development.
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在半侧向发育过程中,前后轴通过早期的典型Wnt信号传导模式。

DOI:
10.1371/journal.pbio.2003698
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发表时间:
2018-01
期刊:
影响因子:
9.8
通讯作者:
Lowe CJ
Lowe CJ
中科院分区:
生物学1区
文献类型:
--
作者:
Darras S;Fritzenwanker JH;Uhlinger KR;Farrelly E;Pani AM;Hurley IA;Norris RP;Osovitz M;Terasaki M;Wu M;Aronowicz J;Kirschner M;Gerhart JC;Lowe CJ

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Wnt家族的分泌蛋白已被提出在双侧前后(A/P)轴的早期特化中发挥保守的作用。这一假说主要基于脊椎动物胚胎发生以及涡虫再生和稳态的数据,表明经典Wnt(cWnt)信号传导赋予细胞沿A/P轴沿着的位置信息。在这些门之外,强烈支持cWnt信号传导在抑制前命运中的保守作用,但很少比较支持在促进后命运中的保守作用。我们通过研究cWnt信号在半索动物囊舌鱼(Saccoglossus kowalevskii)的A/P轴沿着早期模式化过程中的作用来进一步检验这一假设。我们克隆并研究了S. kowalevskii在发育早期沿着许多分泌的Wnt修饰物。13种Wnt配体中有11种在重叠结构域中外胚层表达,主要在后部,Wnt拮抗剂主要定位于前部外胚层,其模式使人联想到它们在脊椎动物胚胎中的分布。过表达和敲低实验,结合胚胎学操作,确立了cWnt信号传导在S.科瓦列夫斯基。然而,令人惊讶的是,由后部Hox基因定义的末端后部命运在晚期囊胚和早期原肠胚的A/P轴的早期建立期间对cWnt水平的操纵没有反应。我们建立了实验支持的保守作用Wnt信号在早期规格的A/P轴在后口体计划多样化,并进一步建立支持的祖先的作用,这条通路在早期进化的双侧A/P轴。我们发现cWnt在抑制前部命运和促进中间轴命运中的作用得到了强有力的支持,但我们没有发现cWnt信号在S中最后轴命运的早期特化中起作用的证据。科瓦列夫斯基。这种后自主性可能是早期后口轴特化的保守特征。前后(A/P)轴是双侧动物的保守特征,在前部由头部定义,在后部由躯干定义。分泌的Wnt蛋白家族及其拮抗剂在许多双侧性动物的早期发育过程中在建立该轴中发挥保守的作用。Wnt信号传导在A/P轴特化中的作用的广泛接受的模型是通过建立简单的活性梯度,由此高水平的Wnt导致后命运,低水平的Wnt导致前命运。在这项研究中,我们进一步测试这个模型,检查的作用,Wnt信号在橡子蠕虫,一个代表的半脊索动物,属于超门Deuterostomia沿着脊索动物。我们发现强有力的证据支持的假设,Wnt信号抑制前的命运,并促进更多的尾的命运外胚层,以类似的方式在脊椎动物中枢神经系统的发展。然而,我们发现,最后的领土建立独立的Wnt信号,这是不一致的Wnt功能的A/P模式的流行模型。我们的结论是,这些数据是不一致的脊椎动物图案的数据,并可能代表一个保守的功能后口轴图案。
The Wnt family of secreted proteins has been proposed to play a conserved role in early specification of the bilaterian anteroposterior (A/P) axis. This hypothesis is based predominantly on data from vertebrate embryogenesis as well as planarian regeneration and homeostasis, indicating that canonical Wnt (cWnt) signaling endows cells with positional information along the A/P axis. Outside of these phyla, there is strong support for a conserved role of cWnt signaling in the repression of anterior fates, but little comparative support for a conserved role in promotion of posterior fates. We further test the hypothesis by investigating the role of cWnt signaling during early patterning along the A/P axis of the hemichordate Saccoglossus kowalevskii. We have cloned and investigated the expression of the complete Wnt ligand and Frizzled receptor complement of S. kowalevskii during early development along with many secreted Wnt modifiers. Eleven of the 13 Wnt ligands are ectodermally expressed in overlapping domains, predominantly in the posterior, and Wnt antagonists are localized predominantly to the anterior ectoderm in a pattern reminiscent of their distribution in vertebrate embryos. Overexpression and knockdown experiments, in combination with embryological manipulations, establish the importance of cWnt signaling for repression of anterior fates and activation of mid-axial ectodermal fates during the early development of S. kowalevskii. However, surprisingly, terminal posterior fates, defined by posterior Hox genes, are unresponsive to manipulation of cWnt levels during the early establishment of the A/P axis at late blastula and early gastrula. We establish experimental support for a conserved role of Wnt signaling in the early specification of the A/P axis during deuterostome body plan diversification, and further build support for an ancestral role of this pathway in early evolution of the bilaterian A/P axis. We find strong support for a role of cWnt in suppression of anterior fates and promotion of mid-axial fates, but we find no evidence that cWnt signaling plays a role in the early specification of the most posterior axial fates in S. kowalevskii. This posterior autonomy may be a conserved feature of early deuterostome axis specification. The anteroposterior (A/P) axis is a conserved feature of bilateral animals and is defined in the anterior by a head and in the posterior by a trunk. The secreted family of Wnt proteins and their antagonists play a conserved role in setting up this axis during early development in many bilaterians. The widely accepted model for the role of Wnt signalling in A/P axis specification is by the establishment of a simple activity gradient whereby high levels of Wnt lead to posterior fates and low levels to anterior fates. In this study we further test this model, examining the role of Wnt signaling in the acorn worm, a representative of hemichordates that belongs to the superphylum Deuterostomia along with chordates. We find strong evidence supporting the hypotheses that Wnt signaling represses anterior fates and promotes more caudal fates in the ectoderm, in a similar way to central nervous system development in vertebrates However, we find that the most posterior territory is established independently of Wnt signalling, which is inconsistent with the prevailing model of Wnt function in A/P patterning. We conclude that these data are not inconsistent with vertebrate patterning data and may represent a conserved feature of deuterostome axis patterning.
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