Proximo-distal patterning in the Drosophila appendages

描述（由申请人提供）：该项目的长期目标是了解细胞间信号传导系统如何在发育过程中与区域表达的转录因子相互作用，以产生正确比例和图案的身体部位。将使用的实验系统是果蝇，果蝇。这些实验的出发点是两个基因，homothorax和extradenticle，这是重要的指定的身份近端部分的附件在苍蝇。这些基因似乎限制或修改活动的信号传导途径，已知在附件的发展。齿外体和同胸都编码含有同源结构域的转录因子。然而，在有同胸的情况下，齿外体蛋白仅为核蛋白。在几种组织中，Homothorax和Extradenticle与teashirt基因编码的含锌指的转录因子共表达，在眼睛中，这三种蛋白质与eyeless基因编码的另一种同源结构域蛋白共表达。（1）确定同胸鸟控制外齿核定位的机制;（2）描述同胸鸟和胸毛在翅和眼发育中的作用;（3）表征在腿发育期间参与抑制HTH表达的基因，和（4）表征通过正向遗传筛选鉴定的新基因在苍蝇附肢的近端-远端模式中的作用。同胸和齿外体都有脊椎动物同源物，当错误表达时，可能导致白血病，这表明它们在调节脊椎动物生长和发育中也起作用。此外，这些因子的转录和转录后调控在脊椎动物和果蝇肢体发育中似乎相似，这表明它们的许多功能也可能是保守的。因此，了解它们在苍蝇发育中的基本功能，应该会产生与白血病相关的信息，以及可能发生在脊椎动物肢体发育中的缺陷。

DESCRIPTION (provided by applicant): The long-term goals of this project are to understand how cell-to-cell signaling systems interface with regionally expressed transcription factors during development to generate correctly proportioned and patterned body parts. The experimental system that will be used is the fruit fly, Drosophila melanogaster. The starting point for these experiments are two genes, homothorax and extradenticle, that are important for specifying the identity of the proximal portion of the appendages in flies. These genes appear to limit or modify the activities of signaling pathways known to operate during appendage development. Both extradenticle and homothorax encode homeodomain-containing transcription factors. However, Extradenticle protein is only nuclear in the presence of Homothorax. In several tissues, Homothorax and Extradenticle are co-expressed with a Zn-finger-containing transcription factor encoded by the teashirt gene and, in the eye, these three proteins are co-expressed with another homeodomain protein encoded by the eyeless gene.The specific aims for this funding period are to: (1) determine the mechanism by which Extradenticle's nuclear localization is controlled by Homothorax, (2) characterize the roles of homothorax and teashirt in wing and eye development, (3) characterize the genes involved in repressing hth expression during leg development, and (4) characterize the role of novel genes, identified by a forward genetic screen, in proximo-distal patterning in the fly appendages. homothorax and extradenticle both have vertebrate homologs that, when misexpressed, can contribute to leukemias, suggesting that they also play a role in regulating growth and development in vertebrates. In addition, the transcriptional and post-transcriptional regulation of these factors appears similar in vertebrate and fly limb development, suggesting that many of their functions may also be conserved. An understanding of their basic functions in fly development should therefore generate information that is relevant to leukemia, as well as to defects that can occur in vertebrate limb development.