Myelopoiesis in the zebrafish, Danio rerio
Myelopoiesis in the zebrafish, Danio rerio
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DOI：
10.1182/blood.v98.3.643
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发表时间：
2001-08-01
期刊：
影响因子：
20.3
通讯作者：
Look, AT
中科院分区：
文献类型：
--
作者：
Bennett, CM;Kanki, JP;Look, AT
全基因组化学诱变筛选斑马鱼（Danio rerio）导致了新的基因影响脊椎动物红细胞生成的鉴定。在确定这种方法是否也可用于阐明骨髓生成的分子遗传学时，发现斑马鱼肾脏中骨髓前体的发育层次与人类骨髓中的相似。斑马鱼的中性粒细胞类似于人类的中性粒细胞，具有分叶核和髓过氧化物酶阳性的细胞质颗粒。斑马鱼同源的人髓过氧化物酶（MPO）基因，这是特定的中性粒细胞谱系的细胞，被克隆和用于合成反义RNA探针的斑马鱼胚胎的原位杂交分析。表达斑马鱼MPO的粒细胞在受精后18小时（hpf）在后中间细胞团（ICM）和20 hpf前卵黄囊中首次明显。到24 hpf时，在ICM和发育中的血管系统内观察到沿着的MPO表达细胞。因此，mpo基因应该提供一个有用的分子探针，用于鉴定斑马鱼突变体的缺陷，在粒细胞生成。斑马鱼同源物的表达也在其他2种哺乳动物造血基因中进行了检查，Pu. 1似乎在正常哺乳动物骨髓发育中启动定型步骤，L-Plastin是一种由人单核细胞和巨噬细胞表达的基因。结果表明，这些基因的时空表达模式的高度保守的斑马鱼和哺乳动物之间。形态学和分子遗传学的证据支持斑马鱼作为一个信息模型系统的研究正常和异常的人类骨髓。
Genome-wide chemical mutagenesis screens in the zebrafish (Danio rerio) have led to the identification of novel genes affecting vertebrate erythropoiesis. In determining if this approach could also be used to clarify the molecular genetics of myelopoiesis, it was found that the developmental hierarchy of myeloid precursors in the zebrafish kidney is similar to that in human bone marrow. Zebrafish neutrophils resembled human neutrophils, possessing segmented nuclei and myeloperoxidase-positive cytoplasmic granules. The zebrafish homologue of the human myeloperoxidase (MPO) gene, which is specific to cells of the neutrophil lineage, was cloned and used to synthesize antisense RNA probes for in situ hybridization analyses of zebrafish embryos. Granulocytic cells expressing zebrafish mpo were first evident at 18 hours after fertilization (hpf) in the posterior intermediate cell mass (ICM) and on the anterior yolk sac by 20 hpf. By 24 hpf, mpo-expressing cells were observed along the ICM and within the developing vascular system. Thus, the mpo gene should provide a useful molecular probe for identifying zebrafish mutants with defects in granulopoiesis. The expression of zebrafish homologues was also examined in 2 other mammalian hematopoietic genes, Pu.1, which appears to initiate a commitment step in normal mammalian myeloid development, and L-Plastin, a gene expressed by human monocytes and macrophages. The results demonstrate a high level of conservation of the spatio-temporal expression patterns of these genes between zebrafish and mammals. The morphologic and molecular genetic evidence presented here supports the zebrafish as an informative model system for the study of normal and aberrant human myelopoiesis.