Wnt5b-Ryk pathway provides directional signals to regulate gastrulation movement.

Wnt5b-Ryk pathway provides directional signals to regulate gastrulation movement.
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DOI:
10.1083/jcb.200912128
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发表时间:
2010-07-26
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Slusarski DC
Slusarski DC
中科院分区:
其他
文献类型:
--
作者:
Lin S;Baye LM;Westfall TA;Slusarski DC

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可溶性配体Wnt 5 b排斥表达Ryk(与酪氨酸激酶相关)受体的细胞,在原肠胚形成期间建立定向运动。非典型Wnt在很大程度上被认为是脊椎动物细胞通过卷曲(Fz)运动的许可线索。除了Fz之外,已知Wnt配体通过与酪氨酸激酶(Ryk)相关的替代受体来调节神经突生长。然而,胚胎发生过程中的Wnt-Ryk信号转导不太清楚。在这项研究中,我们报告的作用Wnt 5 b作为一个指导性的线索,通过Ryk调节原肠胚运动。在斑马鱼中,Ryk缺陷损害Wnt 5 b诱导的Ca 2+活性和定向细胞运动。Wnt 5 b-Ryk信号转导促进极化细胞突起。在Wnt 5 b刺激后,Fz 2而不是Ryk将Dishevelled募集到细胞膜上,这表明Fz 2和Ryk介导不同的途径。使用共培养测定产生定向Wnt 5 b线索,我们证明Ryk表达细胞迁移远离Wnt 5 b来源。我们得出结论,全长Ryk传达Wnt 5 b信号在原肠胚形成过程中的定向方式。
The soluble ligand Wnt5b repels cells expressing the Ryk (related to tyrosine kinase) receptor, establishing directional motility during gastrulation. Noncanonical Wnts are largely believed to act as permissive cues for vertebrate cell movement via Frizzled (Fz). In addition to Fz, Wnt ligands are known to regulate neurite outgrowth through an alternative receptor related to tyrosine kinase (Ryk). However, Wnt–Ryk signaling during embryogenesis is less well characterized. In this study, we report a role for Wnt5b as an instructive cue to regulate gastrulation movements through Ryk. In zebrafish, Ryk deficiency impairs Wnt5b-induced Ca2+ activity and directional cell movement. Wnt5b–Ryk signaling promotes polarized cell protrusions. Upon Wnt5b stimulation, Fz2 but not Ryk recruits Dishevelled to the cell membrane, suggesting that Fz2 and Ryk mediate separate pathways. Using co-culture assays to generate directional Wnt5b cues, we demonstrate that Ryk-expressing cells migrate away from the Wnt5b source. We conclude that full-length Ryk conveys Wnt5b signals in a directional manner during gastrulation.
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