斑马鱼cmyb基因调控原始髓系造血发育机理的研究

项目名称： 斑马鱼cmyb基因调控原始髓系造血发育机理的研究

项目编号： No.31271574

项目类型： 面上项目

立项/批准年度： 2013

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： 80万元

中文摘要： 原始髓系造血是脊椎动物胚胎发育的重要步骤，尽管已知数个转录因子参与调控，但原始髓系造血调控机制目前仍不明确。我们通过分析前期筛选到的斑马鱼原始髓系造血缺陷的突变体cmybhkz3，发现该突变体的髓系祖细胞的产生以及巨噬细胞系的发育不受影响，而髓系祖细胞向中性粒细胞的定向发育过程受到了阻遏。因此，我们推测cMyb参与调控了原始中性粒细胞的分化成熟过程。迄今未见有关cMyb在动物模型中调控原始粒系细胞发育的报道，本项目拟通过以下研究来揭示cMyb的调控机制：运用细胞学、遗传学、分子生物学以及生物化学等方法研究cMyb在原始中性粒细胞发育中的细胞学功能和机理、调控下游基因的分子机制、以及在遗传通路中与转录因子Runx1、C/ebp1的互作关系。该研究有望揭示未曾报道的原始髓系细胞发育的分子机理及遗传学通路，并为探索人类相关疾病的机理做出贡献。

中文关键词： 斑马鱼；原始髓系造血；中性粒细胞；cMyb；Cebp1

英文摘要： Primitive myelopoiesis is a key process for vertebrate embryonic development. Despite of several transcription factors are found to be involved in myelopoiesis, the mechanism of primitive myelopoiesis is unclear due to lack of genetic mutants. Based on the the study of a myeloid defective zebrafish mutant cmybhkz3, we showed that cmybhkz3 mutants had a reduction in neutrophil number, but preserved normality in macrophage lineage, as well as myeloid progenitors. It is indicated that cMyb 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 defective embryonic granulopoiesis in cmybhkz3, and elucidate the genetic and molecular cMyb-Runx1 axis and cMyb-C/ebp1 axis during embryonic myeloid development. Our study establishes a regulatory hierarchy during myelopoiesis in which lineage is unique controlled by cMyb.

英文关键词： zebrafish；primitive myelopoiesis；neutrophil；cMyb；Cebp1