Wnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis

Hsin-Yi Henry Ho; Michael W. Susman; Jay B. Bikoff; Yun Kyoung Ryu; Andrea M. Jonas; Linda Hu; Rejji Kuruvilla; Michael Eldon Greenberg

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Wnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis

机译：Wnt5a-Ror-混乱的信号传导构成控制组织形态发生的核心发育途径

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Wnts make up a large family of extracellular signaling molecules that play crucial roles in development and disease. A subset of noncanonical Wnts signal independently of the transcription factor p-catenin by a mechanism that regulates key morphogenetic movements during embryogenesis. The best characterized noncanonical Wnt, Wnt5a, has been suggested to signal via a variety of different receptors, including the Ror family of receptor tyrosine kinases, the Ryk receptor tyrosine kinase, and the Frizzled seventransmembrane receptors. Whether one or several of these receptors mediates the effects of Wnt5a in vivo is not known. Through loss-of-function experiments in mice, we provide conclusive evidence that Ror receptors mediate Wnt5a-dependent processes in vivo and identify Dishevelled phosphorylation as a physiological target of Wnt5a-Ror signaling. The absence of Ror signaling leads to defects that mirror phenotypes observed in Wnt5a null mutant mice, including decreased branching of sympathetic neuron axons and major defects in aspects of embryonic development that are dependent upon morphogenetic movements, such as severe truncation of the caudal axis, the limbs, and facial structures. These findings suggest that Wnt5a-Ror-Dishevelled signaling constitutes a core noncanonical Wnt pathway that is conserved through evolution and is crucial during embryonic development.

机译：Wnt构成了一大类细胞外信号分子，它们在发育和疾病中起关键作用。非经典Wnts的子集通过调节胚胎发生过程中关键形态发生运动的机制独立于转录因子p-catenin发出信号。已提出最有特征的非经典Wnt Wnt5a通过多种不同的受体发出信号，包括受体酪氨酸激酶的Ror家族，Ryk受体酪氨酸激酶和卷曲的七跨膜受体。这些受体中的一种还是几种在体内介导Wnt5a的作用尚不清楚。通过小鼠的功能丧失实验，我们提供了确凿的证据，证明Ror受体在体内介导Wnt5a依赖性过程，并将Disheveled磷酸化确定为Wnt5a-Ror信号传导的生理靶标。 Ror信号的缺乏会导致缺陷，这些缺陷反映出在Wnt5a无效突变小鼠中观察到的表型缺陷，包括交感神经元轴突的分支减少以及胚胎发育方面的主要缺陷，这些缺陷取决于形态发生运动，例如尾轴的严重截断，肢体和面部结构。这些发现表明，Wnt5a-Ror-Dishevelled信号传导构成了一个核心的非经典Wnt途径，该途径通过进化得以保存，并且在胚胎发育过程中至关重要。

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来源
《Proceedings of the National Academy of Sciences of the United States of America》 |2012年第11期|p.4044-4051|共8页
作者
Hsin-Yi Henry Ho; Michael W. Susman; Jay B. Bikoff; Yun Kyoung Ryu; Andrea M. Jonas; Linda Hu; Rejji Kuruvilla; Michael Eldon Greenberg;
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作者单位

Department of Neurobiology, Harvard Medical School, Boston, MA 02115;

Department of Neurobiology, Harvard Medical School, Boston, MA 02115;

Department of Neurobiology, Harvard Medical School, Boston, MA 02115;

Department of Biology, Johns Hopkins University, Baltimore, MD 21218;

Department of Neurobiology, Harvard Medical School, Boston, MA 02115;

Department of Neurobiology, Harvard Medical School, Boston, MA 02115;

Department of Biology, Johns Hopkins University, Baltimore, MD 21218;

Department of Neurobiology, Harvard Medical School, Boston, MA 02115;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类
关键词
noncanonical wnt signaling; Ror1; Ror2; tissue elongation axon branching;

机译：非规范的wnt信号;Ror1;Ror2;组织伸长轴突分支;

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Wnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis

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