Analysis of the role of the jing zinc finger in tyrosine kinase pathways in the Drosophila trachea

管状器官的形成是动物发育中的一件大事。研究果蝇胚胎中呼吸器官(气管)的形成提供了关于细胞迁移、细胞形状变化和管状结构的宝贵信息。所有这些过程都有助于形成管子，使整个胚胎中的气流和气体与组织交换。这种分枝结构的模式是遗传硬连线的，涉及其许多发育阶段的基因可以很容易地使用果蝇模型系统进行研究和操作。我的实验室已经证明，Jing基因是胚胎气管分支的关键调节因子。Jing基因调控的生长因子控制细胞的迁移、侵袭和小管的形成。它们还诱导血管生成，后者在癌症的早期转移中发挥关键作用。我们将利用遗传学、细胞生物学和生化方法来确定Jing如何控制生长因子。*Jing基因产物负责激活气管发育过程中的其他基因。当Jing发生突变时，气管细胞不会产生适量的生长因子，细胞也不能正常运动来产生分支。我们将根据Jing启动子中的位点线索，确定哪些基因在不同的发育时期控制Jing的表达。我们还将利用生化和遗传方法确定Jing如何控制生长因子水平。预计这些研究将揭示控制血管结构(如人类肺部和癌症)中细胞迁移的新分子机制。

The formation of tubular organs is a major event in animal development.  Studying the formation of the respiratory organ (trachea) in fruit fly embryos has provided invaluable information about cell migration, changes in cell shape and tubular structures.  All these processes contribute to the formation of tubes that allow airflow and gas exchange with tissues throughout the embryo.  The pattern of this branched structure is genetically hardwired and the genes involved in its many stages of development can be easily studied and manipulated using the fruit fly model system. My laboratory has shown that to the jing gene is a key regulator of embryonic tracheal branching.  The growth factors regulated by Jing control cellular migration, invasion and tubule formation.  They also induce angiogenesis which plays a key role in early metastasis in cancer.  We will determine how Jing controls growth factors using genetics, cell biology and biochemical approaches.  The jing gene product is responsible for activating other genes during tracheal development.  When jing is mutated, tracheal cells do not produce proper amounts of growth factors and cells do not move properly to make the branches.  We will determine which genes control the expression of jing at different times of development using clues from sites in its promoter.  We will also determine how jing controls growth factor levels using biochemical and genetic approaches.  It is anticipated that these studies will reveal new molecular mechanisms controlling cell migration in vascular structures such as the human lungs and cancerous tumours.