Müller H A, Samanta R, Wieschaus E
Institut für Genetik, Heinrich Heine Universität Düsseldorf, Germany. muellear@uni-duesseldorf.
Development. 1999 Feb;126(3):577-86. doi: 10.1242/dev.126.3.577.
Wingless signaling plays a central role during epidermal patterning in Drosophila. We have analyzed zygotic requirements for Wingless signaling in the embryonic ectoderm by generating synthetic deficiencies that uncover more than 99% of the genome. We found no genes required for initial wingless expression, other than previously identified segmentation genes. In contrast, maintenance of wingless expression shows a high degree of zygotic transcriptional requirements. Besides known genes, we have identified at least two additional genomic regions containing new genes involved in Wingless maintenance. We also assayed for the zygotic requirements for Wingless response and found that no single genomic region was required for the cytoplasmic accumulation of Armadillo in the receiving cells. Surprisingly, embryos homozygously deleted for the candidate Wingless receptor, Dfrizzled2, showed a normal Wingless response. However, the Armadillo response to Wingless was strongly reduced in double mutants of both known members of the frizzled family in Drosophila, frizzled and Dfrizzled2. Based on their expression pattern during embryogenesis, different Frizzled receptors may play unique but overlapping roles in development. In particular, we suggest that Frizzled and Dfrizzled2 are both required for Wingless autoregulation, but might be dispensable for late Engrailed maintenance. While Wingless signaling in embryos mutant for frizzled and Dfrizzled2 is affected, Wingless protein is still internalized into cells adjacent to wingless-expressing cells. Incorporation of Wingless protein may therefore involve cell surface molecules in addition to the genetically defined signaling receptors of the frizzled family.
无翅信号通路在果蝇表皮模式形成过程中发挥着核心作用。我们通过构建覆盖基因组99%以上区域的合成缺失突变体，分析了胚胎外胚层中无翅信号通路的合子需求。我们发现，除了先前鉴定出的参与体节形成的基因外，没有其他基因是初始无翅表达所必需的。相比之下，无翅表达的维持显示出高度的合子转录需求。除了已知基因外，我们还鉴定出至少两个额外的基因组区域，其中包含参与无翅维持的新基因。我们还检测了无翅信号应答的合子需求，发现没有单个基因组区域是受体细胞中犰狳蛋白胞质积累所必需的。令人惊讶的是，候选无翅受体Dfrizzled2纯合缺失的胚胎表现出正常的无翅信号应答。然而，在果蝇卷曲蛋白家族的两个已知成员卷曲蛋白和Dfrizzled2的双突变体中，犰狳蛋白对无翅的应答显著降低。基于它们在胚胎发育过程中的表达模式，不同的卷曲蛋白受体可能在发育中发挥独特但重叠的作用。特别是，我们认为卷曲蛋白和Dfrizzled2都是无翅自调控所必需的，但对于后期 engrailed 蛋白的维持可能是可有可无 的。虽然在卷曲蛋白和Dfrizzled2突变的胚胎中无翅信号通路受到影响，但无翅蛋白仍能内化到与无翅表达细胞相邻的细胞中。因此，除了卷曲蛋白家族的遗传定义的信号受体外，无翅蛋白的内化可能还涉及细胞表面分子。
