Genetic Dissection of Drosophila Hematopoiesis

果蝇造血的遗传解剖

• 批准号: 6917592
• 负责人: UTPAL BANERJEE
• 金额: $ 51.92万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-10 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6917592
• 关键词: Drosophilidae; arthropod genetics; biological signal transduction; cell population study; developmental genetics; gene mutation; genetic models; genetic screening; growth factor receptors; hematopoiesis; hematopoietic stem cells; immunogenetics; molecular /cellular imaging; platelet derived growth factor; protein tyrosine kinase; transcription factor; vascular endothelial growth factors

DESCRIPTION (provided by applicant): Drosophila melanogaster has been acknowledged as a premier genetic model system for understanding gene function, developmental networks and molecular basis for genetic disorders including cancers. Drosophila has blood cells or hemocytes that are important for innate immune functions as well as tissue remodeling and wound healing. We initiated a molecular genetic analysis of Drosophila hematopoiesis with the goal to understand the relationship of this process to vertebrate blood development and disorders such as Leukemia. We found that a gene sharing similarity to the Acute Myeloid Leukemia (AML1) protein is essential for the development of 1 of the hemocyte types in Drosophila, called crystal cells. This work led to a lineage diagram for Drosophila hematopoiesis that showed several conserved components. Also the strategies for this development are conserved with similar signaling pathways involved in Drosophila and vertebrate hematopoiesis. More remarkably, concepts such as a common precursor for vascular and blood cells (hemangioblasts) are also conserved. In this proposal, we will first further analyze the functions of the conserved Notch/ PDGF-VEGF receptor/JAK-STAT pathways in Drosophila hematopoieis. We will develop microscopic imaging methods to analyze the hematopoietic process at a single cell level. We will find the molecular basis for the asymmetry that allows hemangioblast divisions to create mixed cell types. And finally, we will analyze novel genes identified from a genetic screen and initiate new genetic screens to identify precursor and possibly stem cell populations and novel proteins that are involved in Drosophila and vertebrate blood cell maturation.

描述（由申请人提供）：果蝇已被公认为是理解基因功能，发育网络和包括癌症在内的遗传疾病的基因功能，发育网络和分子基础的主要遗传模型系统。果蝇的血细胞或血细胞对于先天免疫功能以及组织重塑和伤口愈合很重要。我们开始对果蝇造血的分子遗传分析，目的是了解该过程与脊椎动物血液发育和白血病等疾病的关系。我们发现，与急性髓样白血病（AML1）蛋白具有相似性的基因对于果蝇中一种称为晶体细胞的血细胞类型的1种是必不可少的。这项工作导致果蝇造血的谱图图显示了几种保守的成分。同样，这种发展的策略是保守的，与果蝇和脊椎动物造血相似的相似信号通路。更明显的是，诸如血管和血细胞（血管细胞）的常见前体等概念也得到了保守。在此提案中，我们将首先进一步分析果蝇造血中保守的Notch/ PDGF-VEGF受体/ JAK-STAT途径的功能。我们将开发微观成像方法，以分析单个细胞水平的造血过程。我们将找到不对称的分子基础，该分子基础允许血管细胞分裂产生混合细胞类型。最后，我们将分析从遗传筛查中鉴定出的新基因，并启动新的遗传筛选，以鉴定前体以及可能参与果蝇和脊椎动物血细胞成熟的干细胞种群和新型蛋白质。