TISSUE SPECIFICITY OF WINGLESS SIGNALING IN DROSOPHILA

相邻细胞之间的信号传导对于发育过程中的许多细胞命运决定至关重要。 令人惊讶的是，相同的分泌信号通常用于不同的组织，以引起明显无关的细胞反应。 我们的目标是更好地了解这种现象背后的分子机制，使用一个相对简单的组织特异性调节果蝇分泌蛋白无翅（Wg）的例子。 在发育中的苍蝇翅膀，Wg是需要的感觉刚毛的形成。然而，在眼睛中，Wg信号传导阻止细胞采用刚毛细胞命运。 两种组织中的刚毛前体细胞都接收到Wg信号，但它们对信号的解释不同。为了了解更多关于Wg信号传导的组织特异性方面，提出了两种方法。 我们已经确定了daughterless（da）基因作为Wg依赖的刚毛抑制的潜在直接目标。 我们将确定这种调节的分子机制，以及Da是否是机翼中Wg信号传导的靶点。 第二种方法是表征两个基因，其突变表型表明它们在组织特异性Wg信号传导中起重要作用。 一个基因编码一种蛋白激酶，该蛋白激酶是Wg调节眼睛中而不是翅膀中刚毛形成所必需的。 激酶的遗传表位分析以及生化表征将确定其与Wg信号通路的已知组分的关系。 第二个基因在眼睛中作为Wg信号传导的正效应子，但它拮抗翅膀中的通路。 该基因将被克隆和测序，以阐明它在Wg信号传导中的作用。 我们期望这两种方法将收敛于一个模型，以解释Wg对刚毛形成的组织特异性控制。Wg是在整个动物界中保守的分泌蛋白（称为Wnt）大家族中最具特征的成员之一。 已发现Wnt在无脊椎动物和脊椎动物的发育中发挥许多重要作用。 此外，Wnt信号转导与小鼠和人类的肿瘤发生有关。 由于Wnt信号转导机制在进化上也是保守的，因此了解果蝇中Wg信号转导的组织特异性机制对其他生物体具有广泛的相关性。

Signaling between neighboring cells is crucial for many cell fate decisions during development. Surprisingly, the same secreted signals are often used in different tissues to elicit apparently unrelated cellular responses. Our goal is to understand better the molecular mechanisms underlying this phenomenon, using a relatively simple example of tissue-specific regulation by the Drosophila secreted protein Wingless (Wg). In the developing fly wing, Wg is required for the formation of sensory bristles. However, in the eye Wg signaling prevents cells from adopting a bristle cell fate. The bristle precursor cells in both tissues receive the Wg signal, but they interpret the signal differently. To learn more about the tissue-specific aspects of Wg signaling, two approachers are proposed. We have identified the daughterless (da) gene as potential direct target of Wg-dependent bristle inhibition in the eye. We will determine the molecular mechanism of this regulation and whether Da is a target of Wg signaling in the wing. The second approach is to characterize two genes whose mutant phenotypes indicate that they play important roles in tissue-specific Wg signaling. One gene encodes a protein kinase that is required for Wg regulation of bristle formation in the eye but not in the wing. Genetic epitasis analysis as well as biochemical characterization of the kinase will determine its relationship to known components of the Wg signaling pathway. The second gene acts as a positive effector of Wg signaling in the eye, but it antagonizes the pathway in the wing. This gene will be cloned and sequenced to elucidate the role it plays in Wg signaling. We expect that the two approaches will converge on a model to explain the tissue- specific control of bristle formation by Wg. Wg is one of the best characterized members of a large family of secreted proteins (known as Wnts) conserved throughout the animal kingdom. Wnts have been found to play many important roles in the development of both invertebrates and vertebrates. In addition, Wnt signaling has been implicated in tumorigenesis in mice and humans. Since the machinery for Wnt signal transduction is also evolutionarily conserved, understanding tissue specific mechanisms of Wg signaling in flies should have broad relevance to other organisms.