斑马鱼Poc1a基因在中性粒细胞发育中的作用及机制研究

项目名称： 斑马鱼Poc1a基因在中性粒细胞发育中的作用及机制研究

项目编号： No.31471378

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 张译月

作者单位： 南方医科大学

项目金额： 85万元

中文摘要： 中性粒细胞成熟分化是脊椎动物造血发育以及非特异性免疫系统建立的重要环节,虽有数个转录因子及消化酶参与调控了中性粒细胞的分化成熟，但胚胎期中性粒细胞的发育成熟的调控机制目前仍不明确。我们前期筛选得到了粒系造血缺陷的nld1(Neutrophil Lineage Deficient 1)斑马鱼突变体，并克隆到了可能的致变基因中心粒蛋白1a（Poc1a），我们的前期结果表明Poc1a调控了中性粒细胞的分化成熟过程：表现为细胞数目不变，但轮廓变圆、颗粒数目减少及颗粒运动性减弱，颗粒中的髓过氧化物酶活性减弱，并且细胞的随机变形运动增强。迄今未见有关Poc1a调控中性粒细胞发育的报道，因此我们将通过分析nld1突变体中性粒细胞的缺陷表型，研究Poc1a在中性粒细胞发育途径中与已知因子的分子间互作及遗传学调控关系，并通过筛选与Poc1a相互作用的蛋白来揭示调控中性粒细胞发育成熟的新的细胞学及分子机理。

中文关键词： 斑马鱼；中性粒细胞发育；细胞分化；Poc1a

英文摘要： Differentiaion and maturation of neutrophil is a key process for vertebrate embrynonic hematopoiesis and non-specific immune system establishment.Despite of several transcritpion factors and digestion proteins are found to be involved in neutrophil differentiation, the mechanism of neutrophil maturation is largely unknown.Based on the study of a neutrophil lineage deficient zebrafish mutant nld1, we showed that nld1 mutants had a no altered neutrophil number, but show more roundness cell shape, reduced granule number and impaired granule motility.By positional cloning, we mapped the causative gene Poc1a.It is indicated that Poc1a acts as a novel factor essential for neutrophil maturation in controlling granulocyte differentiation.In this proposal, we are going to define the cellular and molecular basis for devective granulopoiesis in nld1 mutant lucidate the molecular regulation and genetic interaction of known factors and Poc1a in neutrophil maturation regulatory pathway. Meanwhile, we are going to screen novel Poc1a interaction proteins to reveal new cellular and molecular mechanism in neutrophil maturation. Our study establishes a regulatory hierarchy during neutrophil maturation in which lineage is unique controlled by Poc1a.

英文关键词： zebrafish;neutrophil development;cell differentiation;Poc1a