Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.
Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.
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DOI：
10.1534/g3.113.009522
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发表时间：
2014-04-16
期刊：
影响因子：
--
通讯作者：
Eisenmann DM
中科院分区：
文献类型：
--
作者：
Jackson BM;Abete-Luzi P;Krause MW;Eisenmann DM
Wnt信号通路在后生动物的发育过程中起着重要作用，它调节多种过程，包括细胞命运规范、细胞迁移和干细胞更新。β -catenin依赖性/典型Wnt通路的激活可上调Wnt靶基因的表达，从而介导细胞反应。在秀丽隐杆线虫中，一个典型的Wnt信号通路调节了幼虫发育过程中的几个过程；然而，这一途径的靶基因很少被发现。为了解决这一缺陷，我们采用了一种新的方法，通过过度表达激活的β -连环蛋白，在幼虫生命的特定阶段有条件激活Wnt信号，然后使用微阵列分析来鉴定与对照动物相比表达改变的基因。我们鉴定了166个差异表达基因，其中104个表达上调。一组上调基因在Wnt信号减少或增加的突变体中表达改变；我们认为这些基因是真正的秀丽隐杆线虫Wnt通路的目标。其中有6个基因，包括角质层胶原蛋白基因，bli-1col-38， col-49和col-71。这些基因在正常发育的L4中期达到表达高峰，表明在成体角质层形成中起作用。与这一发现相一致的是，一些基因功能的减少会导致提示角质层功能或完整性缺陷的表型。因此，这项工作已经确定了大量在幼虫生命期间推测的Wnt通路靶基因，包括一小部分可能在成虫角质层合成中起作用的Wnt调节的胶原基因。
The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin−dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.
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