TISSUE SPECIFICITY OF WINGLESS SIGNALING IN DROSOPHILA

在发育过程中，相邻细胞之间的信号传导对许多细胞命运决定至关重要。令人惊讶的是，相同的分泌信号经常在不同的组织中使用，引起明显不相关的细胞反应。我们的目标是利用果蝇分泌蛋白无翼蛋白（Wg）的组织特异性调控的一个相对简单的例子，更好地理解这种现象背后的分子机制。在发育中的苍蝇翅膀中，感觉刚毛的形成需要Wg。然而，在眼睛中，Wg信号阻止细胞采用刚毛细胞的命运。两种组织中的刚毛前体细胞接收到Wg信号，但它们对信号的解释不同。为了更多地了解Wg信号的组织特异性方面，提出了两种方法。我们已经确定了无子代（da）基因作为眼睛中wg依赖性刚毛抑制的潜在直接靶点。我们将确定这种调控的分子机制，以及Da是否是翅膀中Wg信号传导的靶标。第二种方法是描述两个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的基因。一种基因编码一种蛋白激酶，这种蛋白激酶对眼睛的刚毛形成的调节是必需的，而对翅膀的刚毛形成则不需要。遗传外延分析以及激酶的生化表征将确定其与Wg信号通路已知组分的关系。第二个基因在眼睛中作为Wg信号的积极效应者，但它在翅膀中拮抗该途径。该基因将被克隆并测序，以阐明其在Wg信号传导中的作用。我们期望这两种方法将会聚在一个模型上，以解释Wg对刚毛形成的组织特异性控制。Wg是整个动物界保守的一个分泌蛋白大家族（称为wnt）中最具特征的成员之一。wnt已被发现在无脊椎动物和脊椎动物的发育中起着许多重要的作用。此外，Wnt信号还与小鼠和人类的肿瘤发生有关。由于Wnt信号转导的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应该与其他生物具有广泛的相关性。

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.