Genetic Dissection of Drosophila Hematopoiesis

果蝇造血的遗传解剖

• 批准号: 6638785
• 负责人: UTPAL BANERJEE
• 金额: $ 37.54万
• 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 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6638785
• 关键词: Drosophilidae; arthropod genetics; biological signal transduction; cell population study; developmental genetics; genetic screening; hematopoiesis; hematopoietic stem cells; immunogenetics; transcription factor

DESCRIPTION (Applicant's abstract): The study of lineage specification during hematopoiesis in mammals is important due to its relationship to many blood related disorders including Leukemia. However, many fundamental questions regarding the specification of unique fates remain unresolved. Drosophila has a simple hematopoietic system constituting of cell types that function in innate immunity and phagocytosis. A hierarchy of multiple transcription factors that specify hematopoietic lineage in Drosophila have been identified. The GATA factor Serpent is required for all hematopoiesis. Lozenge, which bears similarity to the Acute Myeloid Leukemia protein in humans is required for the development of one blood cell type, the crystal cells in Drosophila. Gcm is required for the development of the plasmatocytes/macrophages. Recently we have established that the Notch receptor and its ligand Serrate are involved in the induction of blood cells in Drosophila. In this proposal, we present a comprehensive analysis of Drosophila hematopoiesis. The role of Serpent in larval hematopoiesis will be studied; the involvement of the Notch pathway in blood cell development will be fully analyzed. The hematopoietic precursor population will be characterized. A comprehensive genetic study will be performed for a possible role of the many known signal transduction cascades in the process of hematopoieis. Finally, genetic screens will identify genes that are involved in Drosophila hematopoiesis. Given the similarity of the known members of this developmental system with proteins with important function in mammalian hematopoiesis, we expect that many of the new genes identified will have relevance to this important developmental process in mammals.

描述（申请人的摘要）：谱系规范期间的研究 哺乳动物中的造血症很重要，因为它与许多血液的关系 相关疾病，包括白血病。但是，许多基本问题 关于独特命运的规范仍未解决。果蝇有一个 简单的造血系统构成了先天性的细胞类型 免疫力和吞噬作用。多个转录因子的层次结构 已经确定了果蝇中的造血谱系。 Gata 所有造血需要因子蛇。带有的lizenge 与人类中的急性髓细胞性白血病蛋白相似。 一种血细胞类型的发展，果蝇中的晶体细胞。 GCM是 浆细胞/巨噬细胞的发展所必需的。最近我们有 确定缺口受体及其配体锯齿涉及 果蝇中血细胞的诱导。在此提案中，我们提出了 果蝇造血的综合分析。蛇在 将研究幼虫造血； Notch路径的参与 血细胞发育将得到充分分析。造血前体 人口将被描述。全面的遗传研究将是 在许多已知信号转导级联反应的可能作用 造血的过程。最后，遗传筛选将确定基因 参与果蝇造血。鉴于已知的相似性 该发育系统的成员具有具有重要功能的蛋白质 哺乳动物造血，我们希望许多新的基因都将 与哺乳动物的这一重要发展过程相关。