Silencing of Smed-βcatenin1 generates radial-like hypercephalized planarians
Silencing of Smed-βcatenin1 generates radial-like hypercephalized planarians
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DOI：
10.1242/dev.020289
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发表时间：
2008-04-01
期刊：
影响因子：
4.6
通讯作者：
Adell, Teresa
中科院分区：
文献类型：
--
作者：
Iglesias, Marta;Luis Gomez-Skarmeta, Jose;Adell, Teresa
在非胚胎过程中，如再生和稳态，对轴建立的分子机制知之甚少。为了解决这个问题，我们着手分析典型的Wnt通路在Planarians中的作用，Planarians是以其非凡的形态可塑性而闻名的扁形虫。经典Wnt信号传导是一种进化上保守的机制，在胚胎发育过程中赋予极性，在大多数双侧体中指定前后（AP）轴，在早期脊椎动物胚胎中指定背腹（DV）轴。β-连环蛋白是该途径中的关键元件，尽管它是也参与细胞-细胞粘附的双功能蛋白。在这里，我们报告的两个β-连环蛋白同源物的特性，从Schmidtea medicinea（Smed-beta catenin 1/2）。Smed-beta catenin 1的功能丧失，而不是Smed-beta catenin 2，在再生和完整的Planarians，产生放射状hypercephalized Planarians中，AP轴消失，但DV轴保持不受影响，代表一个独特的例子，一个惊人的身体对称性转变。放射状细胞肥大的表型证明了在AP轴重建和维持中需要Smed-β连环蛋白1，并支持经典Wnt信号传导在AP轴特化中的保守作用，而β-连环蛋白在DV轴建立中的作用将是脊椎动物的创新。当与存在于每个S中的蛋白质结构域一起考虑时。medicinea β-catenin和爪蟾胚胎中功能测定的结果表明，细胞核积累和轴诱导与Smed-β catenin 1，但不是Smed-β catenin 2，这些数据表明，S.地中海β-连环蛋白可能是功能特化的，只有Smed-beta catenin 1参与Wnt信号传导。
Little is known about the molecular mechanisms responsible for axis establishment during non-embryonic processes such as regeneration and homeostasis. To address this issue, we set out to analyze the role of the canonical Wnt pathway in planarians, flatworms renowned for their extraordinary morphological plasticity. Canonical Wnt signalling is an evolutionarily conserved mechanism to confer polarity during embryonic development, specifying the anteroposterior (AP) axis in most bilaterians and the dorsoventral ( DV) axis in early vertebrate embryos. beta-Catenin is a key element in this pathway, although it is a bifunctional protein that is also involved in cell-cell adhesion. Here, we report the characterization of two beta-catenin homologs from Schmidtea mediterranea (Smed-beta catenin1/2). Loss of function of Smed-beta catenin1, but not Smed-beta catenin2, in both regenerating and intact planarians, generates radial-like hypercephalized planarians in which the AP axis disappears but the DV axis remains unaffected, representing a unique example of a striking body symmetry transformation. The radial-like hypercephalized phenotype demonstrates the requirement for Smed-beta catenin1 in AP axis re-establishment and maintenance, and supports a conserved role for canonical Wnt signalling in AP axis specification, whereas the role of beta-catenin in DV axis establishment would be a vertebrate innovation. When considered alongside the protein domains present in each S. mediterranea beta-catenin and the results of functional assays in Xenopus embryos demonstrating nuclear accumulation and axis induction with Smed-beta catenin1, but not Smed-beta catenin2, these data suggest that S. mediterranea beta-catenins could be functionally specialized and that only Smed-beta catenin1 is involved in Wnt signalling.