REGULATION OF RHODOPSIN GENE EXPRESSION IN DROSOPHILA

色觉依赖于光感受器细胞(PR‘s)中存在的不同视紫红质分子对不同波长光的检测。为了避免感觉重叠，大多数视觉系统已经开发出一种机制，允许每个PR只表达一个视紫红质(Rh)。最近的证据表明，rh基因表达的调节纯粹是转录的，需要PR同一性的位点与亚型特异性元件的结合。最近研究表明，Pax-6通过一种所有rh基因共有的元件对PR的认同性起着重要作用。此外，初步数据表明，转录因子正齿(OTD)对于Rh3、RH5和Rh6的亚型特异性表达是重要的。然而，大多数与PR亚型特异性有关的转录因子尚未被描述。因此，这项建议中描述的研究集中在鉴定和表征参与rh基因表达的转录因子。为了实现这些目标，我们将解决三个具体目标：1)研究Pax-6在PR特异性rh基因表达中的作用；2)鉴定OTD在亚型特异性rh基因表达中的作用；3)寻找参与亚型特异性基因表达的新的转录因子。这些实验将使用各种分子和遗传方法进行。这项工作的成功完成将有助于更好地理解果蝇复眼色觉所必需的视紫红质蛋白家族的调节。有趣的是，Pax-6和OTD的脊椎动物同源物都与视网膜特有的基因表达有关，这些基因产物的突变会导致眼睛特有的疾病，如虹膜缺乏症和视锥细胞杆营养不良。因此，来自这项工作的研究也可能为脊椎动物视网膜形成模式的机制提供洞察力。

Color vision relies on a detection of distinct wavelengths of light by different rhodopsin molecules present in photoreceptor cells (PR's). To avoid sensory overlap, most visual systems have developed a mechanism to allow just one rhodopsin (Rh) to be expressed per PR. Recent evidence has suggested that the regulation of rh gene expression is purely transcriptional, requiring the combination of a site for PR identity together with subtype specificity elements. Pax-6 recently been shown to be important for PR identity through an element common to all rh genes. Furthermore, preliminary data indicates that the transcription factor orthodenticle (otd) is important for subtype-specific expression of rh3, rh5, and rh6. However, most of the transcription factors responsible for PR subtype specificity have not yet been described. Therefore, the studies described in this proposal are focused on identifying and characterizing the transcription factors involved in rh gene expression. To achieve these goals, we will address three specific aims: 1) characterize the role of Pax-6 in PR-specific rh gene expression; 2) characterize the role of otd in subtype- specific rh gene expression; and 3) identify novel transcription factors involved in subtype-specific gene expression. These experiments will be performed using a variety of molecular and genetic approaches. The successful completion of this work will lead to a better understanding of the regulation of the rhodopsin family of proteins necessary for color vision in the Drosophila compound eye. Interestingly, the vertebrate homologs of both Pax-6 and otd have been associated with retina-specific gene expression, and mutations in these gene products result in eye- specific diseases such as aniridia and cone-rod dystrophy. Therefore, studies derived from this work may also provide insight into the mechanisms underlying patterning of the vertebrate retina.