The transcription factors Scl and Lmo2 act together during development of the hemangioblast in zebrafish
The transcription factors Scl and Lmo2 act together during development of the hemangioblast in zebrafish
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DOI：
10.1182/blood-2006-02-003087
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发表时间：
2007-03-15
期刊：
影响因子：
20.3
通讯作者：
Patient, Roger
中科院分区：
文献类型：
--
作者：
Patterson, Lucy J.;Gering, Martin;Patient, Roger
转录因子Scl和Lmo 2对所有血液的发育至关重要。最近在斑马鱼胚胎中也发现了内皮发育对Scl的一个重要的早期需求，支持了以前在sct（-/-）胚状体中的发现。Scl耗竭最显著的表现是背主动脉形成失败，这可能揭示了在生血内皮形成中的作用。我们现在提出的证据表明，斑马鱼胚胎对Lmo 2的要求基本上与Scl相同。重要的造血调节因子的表达丢失、减少或延迟，泛内皮基因表达下调，并且血小板特异性标志物表达丢失。Scl和Lmo 2表型的密切相似性表明，它们在多蛋白复合物内的成血管细胞发育中执行这些早期功能，如红细胞生成所示。与此一致，我们发现scl morphant不能被非Lmo 2结合形式的Scl拯救，但可以被非DNA结合形式拯救，这表明通过经由Lmo 2连接的DNA结合伴侣与靶基因拴系。有趣的是，与其他造血调节因子不同，Scl/Lmo 2复合物似乎不自动调节，因为两个基因的表达都不受另一个基因耗尽的影响。因此，这些关键调节因子的表达依赖于上游调节因子的持续表达，上游调节因子可能包括细胞外信号。
The transcription factors Scl and Lmo2 are crucial for development of all blood. An important early requirement for Scl in endothelial development has also been revealed recently in zebrafish embryos, supporting previous findings in sct(-/-) embryoid bodies. Scl depletion culminates most notably in failure of dorsal aorta formation, potentially revealing a role in the formation of hemogenic endothelium. We now present evidence that the requirements for Lmo2 in zebrafish embryos are essentially the same as for Scl. The expression of important hematopoietic regulators is lost, reduced, or delayed, panendothelial gene expression is down-regulated, and aorta-specific marker expression is lost. The close similarity of the phenotypes for Scl and Lmo2 suggest that they perform these early functions in hemangioblast development within a multiprotein complex, as shown for erythropoiesis. Consistent with this, we find that scl morphants cannot be rescued by a non-Lmo2-binding form of Scl but can be rescued by non-DNA-binding forms, suggesting tethering to target genes through DNA-binding partners linked via Lmo2. Interestingly, unlike other hematopoietic regulators, the Scl/Lmo2 complex does not appear to autoregulate, as neither gene's expression is affected by depletion of the other. Thus, expression of these critical regulators is dependent on continued expression of upstream regulators, which may include cell-extrinsic signals.