Activation of Wnt signaling bypasses the requirement for RTK/Ras signaling during C-elegans vulval induction
Activation of Wnt signaling bypasses the requirement for RTK/Ras signaling during C-elegans vulval induction
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DOI：
10.1101/gad.981602
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发表时间：
2002-05-15
影响因子：
10.5
通讯作者：
Eisenmann, DM
中科院分区：
文献类型：
--
作者：
Gleason, JE;Korswagen, HC;Eisenmann, DM
在秀丽线虫外阴发育过程中，受体酪氨酸激酶/RAS和Notch信号通路的激活导致三个外阴前体细胞(VPC)采用诱导细胞命运。Wnt信号通路也通过调节HOX基因LIN-39在VPC指定的细胞命运中起作用。我们在这里表明，无论是pry-1的突变还是激活的bar-1β-catenin蛋白的表达都会导致过度诱导的表型，其中超过三个VPC采用诱导的细胞命运。这表明编码线虫Axin同源物的Pry-1在VPC中起到Wnt信号的负调节作用。APC同系物APR-1活性的丧失增加了这种过度诱导的表型的外显性，表明APR-1可能在线虫的这一过程中发挥负作用，类似于其他系统中的APC蛋白。POP-1Tcf和LIN-39Hox基因的功能降低抑制了过度诱导的表型。令人惊讶的是，由过度激活的Wnt信号引起的过度诱导表型并不依赖于通过RAS途径的信号。这些数据表明，Wnt信号的过度激活足以导致VPC采用诱导命运，并且典型的Wnt途径可能在线虫外阴诱导过程中发挥重要作用。
During Caenorhabditis elegans vulval development, activation of receptor tyrosine kinase/Ras and Notch signaling pathways causes three vulval precursor cells (VPCs) to adopt induced cell fates. A Wnt signaling pathway also acts in cell fate specification by the VPCs, via regulation of the Hox gene lin-39. We show here that either mutation of pry-1 or expression of an activated BAR-1 beta-catenin protein causes an Overinduced phenotype, in which greater than three VPCs adopt induced cell fates. This indicates that pry-1, which encodes a C. elegans axin homolog, acts as a negative regulator of Wnt signaling in the VPCs. Loss of activity of the APC homolog apr-1 increases the penetrance of this Overinduced phenotype, suggesting that APR-1 may play a negative role in Wnt signaling in this process in C. elegans similar to APC proteins in other systems. The Overinduced phenotype is suppressed by reduction of function of the genes pop-1 TCF and lin-39 Hox. Surprisingly, the Overinduced phenotype caused by hyperactivated Wnt signaling is not dependent on signaling through the Ras pathway. These data suggest that hyperactivation of Wnt signaling is sufficient to cause VPCs to adopt induced fates and that a canonical Wnt pathway may play an important role during C. elegans vulval induction.