Genes Controlling Blood Cell Development in Drosophila

超出所提供的空间。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。对这些复杂的事件至关重要的是各种造血转录因子的协同激活或抑制，这些转录因子组合作用于直接谱系特异性基因表达。在脊椎动物中，根据它们作为血细胞表达基因的反式调节因子的作用，或者它们在特定白血病中作为染色体中断或重排的位点的特征，已经确定了许多这些因素。造血系统也存在于模式生物果蝇中，最近的研究表明，果蝇血细胞发育所需的基因与高等真核生物中发现的某些造血因子具有功能同源性。在转录调节因子方面，利用果蝇遗传学可以快速分析GATA因子Serpent、GATA因子Friend of GATA因子U形和runx相关蛋白Lozenge在血细胞规范和分化中的功能。该提案进一步分析了这些基本调节因子的表达、相互作用和功能方面，并将使用新的造血试剂来筛选这一复杂过程所需的其他基因。研究目标将是表征一个新发现的Serpent的血细胞异构体的表达和功能，确定Serpent和u形在胚胎和幼虫造血的不同细胞事件中的特殊作用，并对晶体细胞规范和分化的基因进行全基因组筛选。由于最近的研究已经证明了控制造血的基因具有令人信服的跨物种保护，这些已知转录调节因子的特征和新发现的遗传参与者应该为控制血细胞产生及其疾病的基本机制提供必要的见解，包括人类白血病。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. 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. PERFORMANCE SITE ========================================Section End===========================================