Genetic Dissection of Drosophila Hematopoiesis

描述(申请者摘要)：关于家谱规范的研究 哺乳动物的造血很重要，因为它与许多血液有关 包括白血病在内的相关疾病。然而，许多根本性的问题 关于独一无二的命运的规定，仍然没有解决。果蝇有一种 由先天发挥功能的细胞类型组成的简单的造血系统 免疫和吞噬作用。多个转录因子的层次结构 果蝇特定的造血谱系已被鉴定。《关贸总协定》 所有的造血术都需要蛇因子。含片，它有 需要与人类急性髓系白血病蛋白相似才能 一种血细胞类型的发育，果蝇体内的晶体细胞。GCM是 是浆细胞/巨噬细胞发育所必需的。最近我们有 证实Notch受体及其配体Serrate参与了 果蝇体内血细胞的诱导。在这项提案中，我们提出了一种 果蝇造血功能的综合分析。蛇在人类社会中的作用 幼虫的造血作用将被研究；Notch途径在 将对血细胞发育情况进行全面分析。造血祖细胞 人口将被描述为。一项全面的基因研究将是 在许多已知的信号转导级联中可能扮演的角色 造血的过程。最后，基因筛查将识别出 都与果蝇的造血有关。鉴于已知事物的相似性 具有重要功能的蛋白质的发育系统的成员 哺乳动物的造血，我们预计许多新发现的基因将 与哺乳动物的这一重要发育过程有关。

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.