Genes Controlling Blood Cell Development in Drosophila

造血是一个复杂的发育过程，涉及干细胞的产生，随后是 多能祖细胞的承诺和不同谱系中成熟血细胞的分化。 这些复杂事件的关键是各种造血细胞的协同激活或抑制 转录因子的组合功能，以指导特定血统的基因表达。在脊椎动物中， 这些因素中的许多都是基于它们作为血细胞表达的反式调节因子的作用而被识别的 特定白血病中染色体中断或重排的基因或其特征。 模式生物果蝇中也存在一种造血系统，最近的研究表明 对果蝇血细胞发育至关重要的基因代表了某些 在高等真核生物中发现的造血因子。关于转录调控因子，苍蝇的利用 遗传学已经允许对GATA因子蛇的快速功能分析，GATA因子U- 形状，和RUNX相关的蛋白质在血细胞规格和分化中。这项建议 进一步分析了这些基本调控因子和小说的表达、相互作用和功能 造血试剂将被用于筛选这一复杂过程所需的额外基因。这个 研究目标将是表征一种新发现的血细胞的表达和功能 蛇的异构体，决定了蛇和U型在不同的细胞事件中的特殊作用 胚胎和幼体造血，并对在晶体细胞中起作用的基因进行全基因组筛选 规范和差异化。因为最近的研究证明了一种令人信服的跨物种 控制造血的基因的保守性，这些已知转录的特征 监管机构和新发现的遗传参与者应该对基本机制提供必要的见解 控制血细胞的产生及其疾病，包括人类的白血病。

Hematopoiesis is a complex developmental process that involves stem cell generation, followed by the commitment of multipotent progenitors and the differentiation of mature blood cells within distinct lineages. Seminal to these intricate events is the coordinated activation or repression of various hematopoietic transcription factors that function combinatorially to direct lineage-specific gene expression. In vertebrates, many of these factors have been identified based on their role as trans-regulators of blood cell expressed genes or their characterization as loci that are chromosomally interrupted or rearranged in specific leukemias. A hematopoietic system also exists in the model organism Drosophila and recent studies have demonstrated that genes essential for blood cell development in the fly represent functional homologues of certain of the hematopoietic factors found in higher eukaryotes. Concerning transcriptional regulators, the utilization of fly genetics has allowed for the rapid functional analysis of the GATA factor Serpent, Friend of GATA factor U- shaped, and Runx-related protein Lozenge in blood cell specification and differentiation. This proposal further analyzes aspects of the expression, interaction, and function of these essential regulators and novel hematopoietic reagents will be used to screen for additional genes required for this complex process. The research objectives will be to characterize the expression and function of a newly discovered blood cell isoform of Serpent, determine the specialized roles of Serpent and U-shaped in the distinct cellular events of embryonic and larval hematopoiesis, and conduct a genome-wide screen for genes that function in crystal cell specification and differentiation. Since recent studies have demonstrated a compelling cross species conservation of genes controlling hematopoiesis, the characterization of these known transcriptional regulators and newly identified genetic players should provide needed insights into fundamental mechanisms controlling blood cell production and their disorders, including leukemia in humans.