Genetic Analysis of Hematopoietic Development

描述（由申请人提供）：我们的目标是了解在胚胎发生过程中调控造血干细胞（HSC）和来自中胚层的血管成血管细胞谱系特化的潜在机制。为了实现这一目标，我们选择了etsrp，造血和血管发育中最早的谱系特异性基因之一，作为切入点，解剖这一过程在斑马鱼。具体而言，我们将分析etsrp在确定性造血中的功能，阐明其特异性表达的调控机制，鉴定和表征其生物学靶点。由于我们拟研究的基因在鱼类和哺乳动物之间高度保守，因此从斑马鱼获得的信息对于理解人类发病机制和设计更好的血液和血管疾病治疗方法应该是有用的。斑马鱼是研究发育、生理学和人类疾病的流行模式生物。我们使用最先进的技术来鉴定和表征斑马鱼血液干细胞和血管祖细胞形成所需的必需新基因。由于这些基因在鱼类和人类之间高度保守，我们的研究将为了解人类造血和血管疾病和辅助设计新的治疗方法提供有价值的信息。

DESCRIPTION (provided by applicant): Our goal is to understand the underlying mechanisms involved in regulating lineage specification of hematopoietic stem cells (HSC) and vascular angioblast cells from mesoderm during embryogenesis. Towards this goal we have chosen etsrp, one of the earliest lineage specific genes involved in hematopoietic and vascular development, as an entry point to dissect this process in zebrafish. Specifically, we will analyze functions of etsrp in definitive hematopoiesis, elucidate mechanisms regulating its specific expression, identify and characterize its biological targets. Since genes we propose to study are highly conserved between fish and mammals information obtained from zebrafish should be useful for understanding human pathogenesis and designing better therapeutics for hematological and vascular diseases. PUBLIC HEALTH RELEVANCE: Zebrafish is a popular model organism for studying development, physiology and human diseases. We use state of the art technologies to identify and characterize essential new genes required for the formation of blood stem cells and vascular progenitors in zebrafish. Since these genes are highly conserved between fish and human our studies will provide valuable information for understanding human hematopoietic and vascular diseases and assisting design of novel therapeutic approaches.