Stainier D Y, Weinstein B M, Detrich H W, Zon L I, Fishman M C
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown 02129, USA.
Development. 1995 Oct;121(10):3141-50. doi: 10.1242/dev.121.10.3141.
Endothelial and hematopoietic cells appear synchronously on the extra-embryonic membranes of amniotes in structures known as blood islands. This observation has led to the suggestion that these two ventral lineages share a common progenitor. Recently, we have shown in the zebrafish, Danio rerio, that a single cell in the ventral marginal zone of the early blastula can give rise to both endothelial and blood cells as well as to other mesodermal cells (Stainier, D. Y. R., Lee, R. K. and Fishman, M. C. (1993). Development 119, 31-40; Lee, R. K. K., Stainier, D. Y. R., Weinstein, B. M. and Fishman, M. C. (1994). Development 120, 3361-3366). Here we describe a zebrafish mutation, cloche, that affects both the endothelial and hematopoietic lineages at a very early stage. The endocardium, the endothelial lining of the heart, is missing in mutant embryos. This deletion is selective as evidenced by the presence of other endothelial cells, for example those lining the main vessels of the trunk. Early cardiac morphogenesis proceeds normally even in the absence of the endocardium. The myocardial cells form a tube that is demarcated into chambers, beats rhythmically, but exhibits a reduced contractility. This functional deficit is likely due to the absence of the endocardial cells, although it may be a direct effect of the mutation on the myocardial cells. Cell transplantation studies reveal that the endothelial defect, i.e. the endocardial deletion, is a cell-autonomous lesion, consistent with the possibility that cloche is part of a signal transduction pathway. In addition, the number of blood cells is greatly reduced in cloche mutants and the hematopoietic tissues show no expression of GATA-1 or GATA-2, two key hematopoietic transcription factors that are first expressed during early embryogenesis. These results show that cloche is involved in the genesis and early diversification of the endothelial and blood lineages, possibly by affecting a common progenitor cell population.
在内胚层动物的胚外膜上，内皮细胞和造血细胞在称为血岛的结构中同步出现。这一观察结果表明，这两个腹侧谱系共享一个共同的祖细胞。最近，我们在斑马鱼（Danio rerio）中发现，早期囊胚腹侧边缘区的单个细胞能够产生内皮细胞、血细胞以及其他中胚层细胞（Stainier, D. Y. R., Lee, R. K. 和 Fishman, M. C. (1993). Development 119, 31 - 40; Lee, R. K. K., Stainier, D. Y. R., Weinstein, B. M. 和 Fishman, M. C. (1994). Development 120, 3361 - 3366）。在此，我们描述了一种斑马鱼突变体——钟形（cloche），它在非常早期的阶段就影响内皮细胞和造血细胞谱系。突变胚胎中缺少心内膜，即心脏的内皮衬里。这种缺失是选择性的，因为其他内皮细胞存在，例如躯干主要血管的衬里细胞。即使没有心内膜，早期心脏形态发生仍正常进行。心肌细胞形成一个被划分成腔室的管子，有节律地跳动，但收缩力降低。这种功能缺陷可能是由于心内膜细胞的缺失，尽管也可能是突变对心肌细胞的直接影响。细胞移植研究表明，内皮缺陷，即心内膜缺失，是一种细胞自主病变，这与钟形可能是信号转导途径的一部分这一可能性相符。此外，钟形突变体中的血细胞数量大幅减少，造血组织不表达GATA - 1或GATA - 2，这是在胚胎早期发育过程中首次表达的两个关键造血转录因子。这些结果表明，钟形可能通过影响一个共同的祖细胞群体，参与内皮细胞和血细胞谱系的发生及早期分化。
