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节中胚层的造血干细胞和血管血管母细胞的谱系规范的潜在机制。为了实现这一目标，我们选择了etsrp基因，这是参与造血和血管发育的最早的谱系特异性基因之一，作为剖析斑马鱼这一过程的切入点。具体地说，我们将分析etsrp在确定的造血中的功能，阐明其特定表达的调控机制，鉴定和表征其生物学靶点。由于我们打算研究的基因在鱼类和哺乳动物之间高度保守，从斑马鱼获得的信息应该有助于了解人类的发病机制，并设计更好的血液和血管疾病治疗方法。公共卫生意义：斑马鱼是研究发育、生理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鉴定斑马鱼血液干细胞和血管祖细胞形成所需的基本新基因。由于这些基因在鱼类和人类之间高度保守，我们的研究将为理解人类的血液和血管疾病提供有价值的信息，并辅助设计新的治疗方法。

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.