Myers Toshia R, Greenwald Iva
Departments of Biological Sciences and Biochemistry and Molecular Biophysics and Howard Hughes Medical Institute, Columbia University, 701 West 168th Street, Room 720, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20368-73. doi: 10.1073/pnas.0709989104. Epub 2007 Dec 10.
The Caenorhabditis elegans vulva has been a valuable paradigm for defining components of signaling pathways and elucidating how signaling events are coordinated to generate a developmental pattern. Vulval precursor cells (VPCs) are induced to adopt vulval fates in the third larval stage by LIN-3, an EGF-like signal produced by the gonad. Competence to respond to the inductive signal requires that the VPCs do not fuse to the major hypodermal syncytium, hyp7. We found that two Wnt-encoding genes, cwn-1 and egl-20, play a major role in preventing fusion of VPCs with hyp7 in the second larval stage. By using tissue-specific rescue of mig-14/Wntless, which is required for the production of Wnt ligands, we found that Wnt signal produced by multiple tissues, including neurons and muscles, promotes or maintains VPC competence before vulval induction. In addition, through laser ablation and genetic analysis, we provide evidence that LIN-3 signal from the gonad also plays a significant role in preventing VPCs from fusing with hyp7. We propose that Wnt signaling plays a permissive role in preventing VPCs from fusing with hyp7 and reevaluate the roles of Wnt and LIN-3/EGF signaling in competence and induction.
秀丽隐杆线虫的阴门是定义信号通路组成部分以及阐明信号事件如何协调以产生发育模式的宝贵范例。在第三幼虫阶段,阴门前体细胞(VPCs)被性腺产生的一种类表皮生长因子(EGF)信号LIN-3诱导,从而获得阴门命运。对诱导信号作出反应的能力要求VPCs不与主要的皮下合胞体hyp7融合。我们发现,两个编码Wnt的基因cwn-1和egl-20在第二幼虫阶段防止VPCs与hyp7融合方面发挥主要作用。通过对mig-14/Wntless进行组织特异性拯救(mig-14/Wntless是产生Wnt配体所必需的),我们发现包括神经元和肌肉在内的多种组织产生的Wnt信号在阴门诱导之前促进或维持VPCs的反应能力。此外,通过激光消融和遗传分析,我们提供证据表明性腺产生的LIN-3信号在防止VPCs与hyp7融合方面也发挥重要作用。我们提出,Wnt信号在防止VPCs与hyp7融合方面起允许作用,并重新评估Wnt和LIN-3/EGF信号在反应能力和诱导过程中的作用。