Primary cilia are not required for normal canonical Wnt signaling in the mouse embryo.
Primary cilia are not required for normal canonical Wnt signaling in the mouse embryo.
复制标题
DOI：
10.1371/journal.pone.0006839
复制
发表时间：
2009-08-31
期刊：
影响因子：
3.7
通讯作者：
Anderson KV
中科院分区：
文献类型：
--
作者：
Ocbina PJ;Tuson M;Anderson KV
小鼠的Sonic hedgehog(Shh)信号需要以微管为基础的细胞器，即初级纤毛。初级纤毛在鞭毛内运输(IFT)过程中被组装和维持，在缺乏IFT所需蛋白质的小鼠突变体中，对Shh的反应被阻断。虽然小鼠IFT突变体的表型与已知的Wnt途径突变体的表型不重叠，但最近的研究数据表明，初级纤毛调节对Wnt信号的反应。因此，我们对突变胚胎和细胞中典型的Wnt信号进行了系统的分析，这些突变胚胎和细胞由于顺行的IFT动蛋白II马达(Kif3a)或IFT复合体B蛋白(Ift172或Ift88)的丢失而缺乏初生纤毛。我们还分析了由于逆行IFT(Dyc2h1)缺陷而导致初级纤毛异常的突变胚胎。小鼠IFT突变体以正常的空间模式和与野生型窝产仔相同的数量水平表达规范的Wnt靶标Axin2，并激活转基因的规范的Wnt报告基因BAT-GAL。同样，来自IFT突变体的小鼠胚胎成纤维细胞(MEF)对添加WNT3a的反应正常。在IFT突变的MEF中，从规范的WNT到非规范的WNT的转换也是正常的，因为野生型和突变的细胞在WNT3a和WNT5a的存在下都不能激活规范的WNT报告。我们的结论是，初级纤毛的丧失或逆行IFT中的缺陷不会影响中期胚胎或胚胎来源的成纤维细胞对Wnt配体的反应。
Sonic hedgehog (Shh) signaling in the mouse requires the microtubule-based organelle, the primary cilium. The primary cilium is assembled and maintained through the process of intraflagellar transport (IFT) and the response to Shh is blocked in mouse mutants that lack proteins required for IFT. Although the phenotypes of mouse IFT mutants do not overlap with phenotypes of known Wnt pathway mutants, recent studies report data suggesting that the primary cilium modulates responses to Wnt signals. We therefore carried out a systematic analysis of canonical Wnt signaling in mutant embryos and cells that lack primary cilia because of loss of the anterograde IFT kinesin-II motor (Kif3a) or IFT complex B proteins (Ift172 or Ift88). We also analyzed mutant embryos with abnormal primary cilia due to defects in retrograde IFT (Dync2h1). The mouse IFT mutants express the canonical Wnt target Axin2 and activate a transgenic canonical Wnt reporter, BAT-gal, in the normal spatial pattern and to the same quantitative level as wild type littermates. Similarly, mouse embryonic fibroblasts (MEFs) derived from IFT mutants respond normally to added Wnt3a. The switch from canonical to non-canonical Wnt also appears normal in IFT mutant MEFs, as both wild-type and mutant cells do not activate the canonical Wnt reporter in the presence of both Wnt3a and Wnt5a. We conclude that loss of primary cilia or defects in retrograde IFT do not affect the response of the midgestation embryo or embryo-derived fibroblasts to Wnt ligands.
登录
查看更多内容
影响因子：
64.8
作者：
Eggenschwiler, JT;Espinoza, E;Anderson, KV
通讯作者：
Anderson, KV
影响因子：
64.8
作者：
Glinka, A;Wu, W;Niehrs, C
通讯作者：
Niehrs, C
影响因子：
64.8
作者：
Ishitani, T;Ninomiya-Tsuji, J;Matsumoto, K
通讯作者：
Matsumoto, K
影响因子：
30.8
作者：
Gerdes, Jantje M.;Liu, Yangfan;Katsanis, Nicholas
通讯作者：
Katsanis, Nicholas
DOI：
10.1083/jcb.141.4.993
发表时间：
1998-05-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cole DG;Diener DR;Himelblau AL;Beech PL;Fuster JC;Rosenbaum JL
通讯作者：
Rosenbaum JL