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系统在发育过程中如何与区域表达的转录因子相结合，以产生正确比例和图案的身体部位。将要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，同质胸和外稃，这是重要的指定的近端部分的附属物在苍蝇的身份。这些基因似乎限制或修改在附属物发育过程中已知的信号通路的活动。外核和同胸都编码含有同域的转录因子。然而，只有在同源胸存在时，外显蛋白才是核的。在一些组织中，Homothorax和extraenticle与一个由衬衫基因编码的含锌手指的转录因子共表达，在眼睛中，这三个蛋白与另一个由无眼基因编码的同源结构域蛋白共表达。该资助期的具体目标是：(1)确定同胸控制extraenticle核定位的机制，(2)表征同胸和衬衫在翅膀和眼睛发育中的作用，(3)表征腿发育过程中抑制hth表达的基因，以及(4)表征通过前向遗传筛选鉴定的新基因在苍蝇附肢近端-远端模式中的作用。同胸和外背都有脊椎动物的同源基因，当错误表达时，可能会导致白血病，这表明它们也在调节脊椎动物的生长和发育中发挥作用。此外，这些因子的转录和转录后调控在脊椎动物和苍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，对它们在果蝇发育中的基本功能的了解，将产生与白血病相关的信息，以及与脊椎动物肢体发育中可能发生的缺陷相关的信息。

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.