Zebrafish scl functions independently in hematopoietic and endothelial development
Zebrafish scl functions independently in hematopoietic and endothelial development
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DOI：
10.1016/j.ydbio.2004.09.004
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发表时间：
2005-01-15
影响因子：
2.7
通讯作者：
Zon, LI
中科院分区：
文献类型：
--
作者：
Dooley, KA;Davidson, AJ;Zon, LI
SCL转录因子对于脊椎动物造血和血管生成至关重要，并且已经被假定诱导成血管细胞、血液和内皮细胞的双能前体。为了研究scl在斑马鱼造血和内皮发育中的作用，我们利用定点反义morpholinos抑制scl mRNA。scl的敲除导致原始和定型造血细胞谱系的丧失。然而，早期造血基因gata 2和lmo 2的表达不受影响，表明造血细胞存在，但不能进一步分化。使用基因表达分析和可视化的血管形成在活的动物窝藏lmo 2启动子-绿色荧光蛋白报告基因转基因（Tg（lmo 2：EGFP）），我们表明，成血管细胞被指定正常的情况下，SCL，但后来的血管生成的缺陷是明显的。虽然scl不是成血管细胞特化所必需的，但外源性scl的强制表达导致造血和内皮基因表达的全部扩增，以及体细胞组织的损失。在cloche和spadetail突变体中，scl的强制表达导致造血组织而不是内皮组织的扩张。令人惊讶的是，在cloche中，lmo 2并没有被scl的过度表达所诱导。总之，这些发现支持scl在造血和内皮发育中的不同作用，在成血管细胞发育的下游。(C)2004年爱思唯尔公司All rights reserved.
The SCL transcription factor is critically important for vertebrate hematopoiesis and angiogenesis, and has been postulated to induce hemangioblasts, bipotential precursors for blood and endothelial cells. To investigate the function of scl during zebrafish hematopoietic and endothelial development, we utilized site-directed, anti-sense morpholinos to inhibit scl mRNA. Knockdown of scl resulted in a loss of primitive and definitive hematopoietic cell lineages. However, the expression of early hematopoietic genes, gata2 and lmo2, was unaffected, suggesting that hematopoietic cells were present but unable to further differentiate. Using gene expression analysis and Visualization of vessel formation in live animals harboring an lmo2 promoter-green fluorescent protein reporter transgene (Tg(lmo2:EGFP)), we show that angioblasts were specified normally in the absence of scl, but later defects in angiogenesis were evident. While scl was not required for angioblast specification, forced expression of exogenous scl caused ail expansion of both hematopoietic and endothelial gene expression, and a loss of somitic tissue. In cloche and spadetail mutants, forced expression of scl resulted in an expansion of hematopoietic but not endothelial tissue. Surprisingly, in cloche, lmo2 was not induced in response to scl over-expression. Taken together, these findings support distinct roles for scl in hematopoietic and endothelial development, downstream of hemangioblast development. (C) 2004 Elsevier Inc. All rights reserved.