Genes Controlling Blood Cell Development in Drosophila

控制果蝇血细胞发育的基因

• 批准号: 6555024
• 负责人: ROBERT A. SCHULZ
• 金额: $ 33.98万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6555024
• 关键词: Drosophilidae; blood cells; cell differentiation; gene expression; genetic regulation; genetic transcription; hematopoiesis; polymerase chain reaction; stem cells; tissue /cell culture; transcription factor; transfection

DESCRIPTION (provided by applicant): 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 Ushaped, 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.

描述（由申请人提供）：造血是一个复杂的发育过程，涉及干细胞的生成，随后是多能祖细胞的分化以及不同谱系内成熟血细胞的分化。这些复杂事件的核心是各种造血转录因子的协调激活或抑制，这些转录因子联合发挥作用以指导谱系特异性基因表达。在脊椎动物中，许多这些因子已根据它们作为血细胞表达基因的反式调节剂的作用或它们作为特定白血病中染色体中断或重排的基因座的特征而被识别。模式生物果蝇中也存在造血系统，最近的研究表明，果蝇中血细胞发育所必需的基因代表了高等真核生物中发现的某些造血因子的功能同源物。关于转录调节因子，利用果蝇遗传学可以对血细胞规范和分化中的 GATA 因子 Serpent、GATA 因子 U 形之友和 Runx 相关蛋白 Lozenge 进行快速功能分析。该提案进一步分析了这些重要调节因子的表达、相互作用和功能，并且新型造血试剂将用于筛选这一复杂过程所需的其他基因。研究目标是表征新发现的Serpent血细胞亚型的表达和功能，确定Serpent和U型在胚胎和幼虫造血的不同细胞事件中的特殊作用，并进行全基因组筛选在晶体细胞规范和分化中发挥作用的基因。由于最近的研究表明控制造血的基因具有令人信服的跨物种保守性，这些已知的转录调节因子和新发现的基因参与者的特征应该为控制血细胞生成及其疾病（包括人类白血病）的基本机制提供所需的见解。