Bef medaka mutant reveals the essential role of c-myb in both primitive and definitive hematopoiesis
Bef medaka mutant reveals the essential role of c-myb in both primitive and definitive hematopoiesis
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DOI：
10.1016/j.ydbio.2010.06.031
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发表时间：
2010-09-15
影响因子：
2.7
通讯作者：
Kudo, Akira
中科院分区：
文献类型：
--
作者：
Moriyama, Akemi;Inohaya, Keiji;Kudo, Akira
脊椎动物的造血功能有两个进化上保守的发展阶段，即胚胎早期短暂的原始造血功能和胚胎后期发生的最终造血功能。贝尼富士（bef）最初是作为medaka突变体分离出来的，其外周血中红细胞数量明显减少。定位克隆显示，bef突变体在c-myb基因上有一个无义突变。先前的研究表明，c-myb是决定性造血所必需的，现在c-myb被广泛用作决定性造血开始的标记基因。为了分析bef突变体的表型，我们与造血细胞的基因标记进行了全贴装原位杂交。牛胚α -珠蛋白和I-plastin表达降低，mpo1和rag1表达完全缺失，提示牛胚不仅在红细胞中存在缺陷，在其他髓系细胞中也存在缺陷，表明其最终造血功能异常。有趣的是，我们观察到胚胎中原始红细胞数量的减少和原始巨噬细胞出现的延迟。这些结果表明c-myb也在原始造血中起作用，潜在地证明了原始造血和最终造血之间的联系。(C) 2010爱思唯尔公司版权所有。
Vertebrate hematopoiesis is characterized by two evolutionally conserved phases of development, i.e., primitive hematopoiesis, which is a transient phenomenon in the early embryo, and definitive hematopoiesis, which takes place in the later stages. Beni fuji (bef) was originally isolated as a medaka mutant that has an apparently reduced number of erythrocytes in its peripheral blood. Positional cloning revealed that the bef mutant has a nonsense mutation in the c-myb gene. Previous studies have shown that c-myb is essential for definitive hematopoiesis, and c-myb is now widely used as a marker gene for the onset of definitive hematopoiesis. To analyze the phenotypes of the bef mutant, we performed whole-mount in situ hybridization with gene markers of hematopoietic cells. The bef embryos showed decreased expression of alpha-globin and I-plastin, and a complete loss of mpo1 and rag1 expression, suggesting that the bef embryos had defects not only in erythrocytes but also in other myeloid cells, which indicates that their definitive hematopoiesis was aberrant. Interestingly, we observed a diminution in the number of primitive erythrocytes and a delay in the emergence of primitive macrophages in the bef embryos. These results suggest that c-myb also functions in the primitive hematopoiesis, potentially demonstrating a link between primitive and definitive hematopoiesis. (C) 2010 Elsevier Inc. All rights reserved.