Genetic Dissection of Drosophila Hematopoiesis

描述（申请人的摘要）： 造血在哺乳动物中是重要的，因为它与许多血液有关。 相关疾病包括白血病。然而，许多基本问题 关于独特命运的具体说明仍然没有解决。果蝇有一个 简单的造血系统，由在先天免疫系统中起作用的细胞类型组成。 免疫和吞噬作用。多个转录因子的层次结构， 已经鉴定出果蝇中特定造血谱系。加塔 Serpent因子是所有造血所必需的。菱形， 与人类急性髓性白血病蛋白的相似性是 果蝇中一种血细胞类型--晶细胞的发育。GCM是 这是浆细胞/巨噬细胞发育所需的。最近我们 确定Notch受体及其配体Serrate参与了 果蝇血细胞的诱导在本提案中，我们提出了一个 果蝇造血的综合分析。蛇的作用 将研究幼虫的造血; Notch途径参与 血细胞发育将被全面分析。所述造血前体 人口将有特点。一项全面的遗传学研究将在 进行了许多已知的信号转导级联的可能作用， 造血的过程。最后，基因筛选将确定基因， 参与果蝇的造血作用。鉴于已知的 这个发育系统的成员与蛋白质具有重要的功能， 哺乳动物造血，我们预计，许多新的基因确定将 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.