Povelones Michael, Howes Rob, Fish Matt, Nusse Roel
Howard Hughes Medical Institute, Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
Genetics. 2005 Dec;171(4):1643-54. doi: 10.1534/genetics.105.045245. Epub 2005 Aug 5.
The frizzled (fz) gene in Drosophila controls two distinct signaling pathways: it directs the planar cell polarization (PCP) of epithelia and it regulates cell fate decisions through Armadillo (Arm) by acting as a receptor for the Wnt protein Wingless (Wg). With the exception of dishevelled (dsh), the genes functioning in these two pathways are distinct. We have taken a genetic approach, based on a series of new and existing fz alleles, for identifying individual amino acids required for PCP or Arm signaling. For each allele, we have attempted to quantify the strength of signaling by phenotypic measurements. For PCP signaling, the defect was measured by counting the number of cells secreting multiple hairs in the wing. We then examined each allele for its ability to participate in Arm signaling by the rescue of fz mutant embryos with maternally provided fz function. For both PCP and Arm signaling we observed a broad range of phenotypes, but for every allele there is a strong correlation between its phenotypic strength in each pathway. Therefore, even though the PCP and Arm signaling pathways are genetically distinct, the set of signaling-defective fz alleles affected both pathways to a similar extent. This suggests that fz controls these two different signaling activities by a common mechanism. In addition, this screen yielded a set of missense mutations that identify amino acids specifically required for fz signaling function.
果蝇中的卷曲（fz）基因控制着两条不同的信号通路：它指导上皮细胞的平面细胞极化（PCP），并通过作为Wnt蛋白无翅（Wg）的受体，通过犰狳（Arm）调节细胞命运决定。除了蓬乱（dsh）之外，在这两条通路中起作用的基因是不同的。我们基于一系列新的和现有的fz等位基因，采用遗传方法来鉴定PCP或Arm信号传导所需的单个氨基酸。对于每个等位基因，我们试图通过表型测量来量化信号传导的强度。对于PCP信号传导，通过计算翅膀中分泌多根刚毛的细胞数量来测量缺陷。然后，我们通过用母源提供的fz功能拯救fz突变胚胎，来检查每个等位基因参与Arm信号传导的能力。对于PCP和Arm信号传导，我们都观察到了广泛的表型，但对于每个等位基因，其在每条通路中的表型强度之间都存在很强的相关性。因此，即使PCP和Arm信号通路在遗传上是不同的，但一组信号缺陷型fz等位基因对两条通路的影响程度相似。这表明fz通过一种共同机制控制这两种不同的信号活动。此外，该筛选产生了一组错义突变，这些突变鉴定出了fz信号功能特别需要的氨基酸。
