Genes Controlling Blood Cell Development in Drosophila

控制果蝇血细胞发育的基因

• 批准号: 7556832
• 负责人: ROBERT A. SCHULZ
• 金额: $ 2.49万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 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 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7556832
• 关键词: Animal Model; Animals; Appendix; Blood; Blood Cells; Cardiac; Cell Lineage; Cell physiology; Cells; Complex; Development; Developmental Process; Disease; Drosophila genus; Drosophila melanogaster; Embryo; Embryonic Development; Essential Genes; Eukaryota; Eukaryotic Cell; Event; Family; Friends; GATA2 transcription factor; Gene Expression; Gene Family; Generations; Genes; Genetic; Genome; Goals; Heart; Hematopoiesis; Hematopoietic; Hematopoietic System; Hematopoietic stem cells; Homeodomain Proteins; Homologous Gene; Human; Investigation; Multipotent Stem Cells; Mus; Numbers; Pathway interactions; Personal Satisfaction; Principal Investigator; Probability; Process; Production; Protein Isoforms; Proteins; Reagent; Regulation; Repression; Research; Role; Seminal; Shapes; Stem cells; System; Vertebrates; base; cardiogenesis; fly; gene conservation; gene discovery; gene function; genome sequencing; insight; leukemia; member; novel; prevent; transcription factor

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.

造血是一个复杂的发育过程，涉及干细胞的产生，然后是 多能祖细胞的定型和不同谱系内成熟血细胞的分化。 对这些复杂事件至关重要的是各种造血系统的协调激活或抑制 组合发挥作用以指导谱系特异性基因表达的转录因子。在脊椎动物中， 其中许多因素已根据其作为血细胞表达的反式调节剂的作用而被识别。 基因或其表征为在特定白血病中染色体中断或重排的基因座。 模式生物果蝇中也存在造血系统，最近的研究表明 果蝇血细胞发育所必需的基因代表某些基因的功能同源物 在高等真核生物中发现的造血因子。关于转录调节因子，利用果蝇 遗传学允许对 GATA 因子 Serpent（GATA 因子 U 的朋友）进行快速功能分析 形状和 Runx 相关蛋白锭剂在血细胞规范和分化中的作用。这个提议 进一步分析这些重要调节因子的表达、相互作用和功能的各个方面，并发现新的 造血试剂将用于筛选这一复杂过程所需的其他基因。这 研究目标是表征新发现的血细胞的表达和功能 蛇的亚型，确定了蛇和 U 形在不同细胞事件中的特殊作用 胚胎和幼虫造血，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。由于最近的研究表明了令人信服的跨物种 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基因参与者应该提供对基本机制的必要见解 控制血细胞的产生及其疾病，包括人类白血病。

项目成果

Gene regulatory networks controlling hematopoietic progenitor niche cell production and differentiation in the Drosophila lymph gland.

• DOI: 10.1371/journal.pone.0041604
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Tokusumi Y;Tokusumi T;Shoue DA;Schulz RA
• 通讯作者: Schulz RA

bantam miRNA is important for Drosophila blood cell homeostasis and a regulator of proliferation in the hematopoietic progenitor niche.

• DOI: 10.1016/j.bbrc.2014.09.109
• 发表时间: 2014-10-24
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Lam V;Tokusumi T;Tokusumi Y;Schulz RA
• 通讯作者: Schulz RA

Characterization of a lamellocyte transcriptional enhancer located within the misshapen gene of Drosophila melanogaster.

• DOI: 10.1371/journal.pone.0006429
• 发表时间: 2009-07-29
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Tokusumi T;Sorrentino RP;Russell M;Ferrarese R;Govind S;Schulz RA
• 通讯作者: Schulz RA

Knockdown of SCF(Skp2) function causes double-parked accumulation in the nucleus and DNA re-replication in Drosophila plasmatocytes.

• DOI: 10.1371/journal.pone.0079019
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kroeger PT Jr;Shoue DA;Mezzacappa FM;Gerlach GF;Wingert RA;Schulz RA
• 通讯作者: Schulz RA

New hemocyte-specific enhancer-reporter transgenes for the analysis of hematopoiesis in Drosophila.

用于分析果蝇造血作用的新血细胞特异性增强子报告基因转基因。

• DOI: 10.1002/dvg.20561
• 发表时间: 2009
• 期刊: Genesis (New York, N.Y. : 2000)
• 作者: Tokusumi,Tsuyoshi;Shoue,DouglasA;Tokusumi,Yumiko;Stoller,JessicaR;Schulz,RobertA
• 通讯作者: Schulz,RobertA