Decoding Dishevelled-Mediated Wnt Signaling in Vertebrate Early Development.

Decoding Dishevelled-Mediated Wnt Signaling in Vertebrate Early Development.
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DOI:
10.3389/fcell.2020.588370
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发表时间:
2020
影响因子:
5.5
通讯作者:
Shi DL
Shi DL
中科院分区:
生物学2区
文献类型:
--
作者:
Shi DL

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紊乱蛋白是Wnt信号通路的关键参与者。它们通过不同的保守结构域抑制Wnt信号并执行细胞功能。由于存在多个旁系同源物、母体转录物的大量积累以及不同Wnt通路的激活,它们在脊椎动物早期发育中的调节作用及其决定通路特异性的机制一直是个谜,在过去的几十年里引起了人们的广泛关注。在不同动物模型中的广泛研究为Wnt信号转导中保守的Dishevelled结构域的结构-功能关系以及Dishevelled亚型在早期发育过程中的意义提供了重要的见解。值得注意的是,分子内和分子间相互作用和Dishevelled剂量在调节Wnt信号传导的特异性中可能是重要的。Dishevelled亚型在发育和疾病中也有不同的和冗余的功能,这可能是由不同的时空表达模式和生化特性以及翻译后修饰引起的。本文就Dishevelled介导的Wnt信号在脊椎动物早期胚胎原肠胚形成和神经胚形成中的作用作一综述。
Dishevelled proteins are key players of Wnt signaling pathways. They transduce Wnt signals and perform cellular functions through distinct conserved domains. Due to the presence of multiple paralogs, the abundant accumulation of maternal transcripts, and the activation of distinct Wnt pathways, their regulatory roles during vertebrate early development and the mechanism by which they dictate the pathway specificity have been enigmatic and attracted much attention in the past decades. Extensive studies in different animal models have provided significant insights into the structure-function relationship of conserved Dishevelled domains in Wnt signaling and the implications of Dishevelled isoforms in early developmental processes. Notably, intra- and inter-molecular interactions and Dishevelled dosage may be important in modulating the specificity of Wnt signaling. There are also distinct and redundant functions among Dishevelled isoforms in development and disease, which may result from differential spatiotemporal expression patterns and biochemical properties and post-translational modifications. This review presents the advances and perspectives in understanding Dishevelled-mediated Wnt signaling during gastrulation and neurulation in vertebrate early embryos.