Specification of arterial, venous, and lymphatic endothelial cells during embryonic development.
Specification of arterial, venous, and lymphatic endothelial cells during embryonic development.
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DOI：
10.14670/hh-25.637
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发表时间：
2010-05
影响因子：
2
通讯作者：
Kume T
中科院分区：
文献类型：
--
作者：
Kume T
在早期胚胎发育中，关于动脉和静脉中分别表达ePhinB2和EphB4的开创性发现为血管研究带来了新的范式，提供了令人信服的证据，表明动脉和静脉内皮细胞在循环开始之前是通过遗传机制建立的。血管内皮生长因子(VEGF)诱导Notch信号基因的表达，包括Notch1及其配体、Delta-like 4(DLL4)，以及Foxc1和FOXC2转录因子直接调节DLL4的表达。在Notch信号被激活后，Notch下游基因Hey1/2在小鼠中或在斑马鱼中陷入僵局，进一步促进动脉分化。另一方面，孤儿核受体COUP-TFII通过抑制包括Nrp1和Notch在内的动脉特异性基因的表达，是静脉指定的决定因素。在动脉和静脉内皮细胞分化后，静脉内皮细胞亚群被认为能够通过逐渐表达转录因子Sox18和Prox1分化为淋巴管内皮细胞，从而获得淋巴管内皮细胞的命运。因此，现在已经证明，动-静脉细胞命运的决定和随后的淋巴管发育是由与关键信号通路和转录因子相关的多步骤调控系统调节的。此外，最近发现了新的信号分子作为这些过程中的额外调节分子。随着动脉、静脉和淋巴管内皮细胞中信号通路和转录网络之间联系的机制基础开始被发现，现在是时候总结这一令人兴奋的主题的文献，并为该领域的未来研究提供展望。
The groundbreaking discovery about arterial and venous expression of ephrinB2 and EphB4, respectively, in early embryonic development has led to a new paradigm for vascular research, providing compelling evidence that arterial and venous endothelial cells are established by genetic mechanisms before circulation begins. For arterial specification, vascular endothelial growth factor (VEGF) induces expression of Notch signaling genes, including Notch1 and its ligand, Delta-like 4 (Dll4), and Foxc1 and Foxc2 transcription factors directly regulate Dll4 expression. Upon activation of Notch signaling, the Notch downstream genes, Hey1/2 in mice or gridlock in zebrafish, further promote arterial differentiation. On the other hand, the orphan nuclear receptor COUP-TFII is a determinant factor for venous specification by inhibiting expression of arterial specific genes, including Nrp1 and Notch. After arterial and venous endothelial cells differentiate, a subpopulation of venous endothelial cells is thought to become competent to acquire lymphatic endothelial cell fate by progressively expressing the transcription factors Sox18 and Prox1 to differentiate into lymphatic endothelial cells. Therefore, it has now evident that arterial-venous cell fate determination and subsequent lymphatic development are regulated by the multi-step regulatory system associated with the key signaling pathways and transcription factors. Furthermore, new signaling molecules as additional regulators in these processes have recently been identified. As the mechanistic basis for a link between signaling pathways and transcriptional networks in arterial, venous and lymphatic endothelial cells begins to be uncovered, it is now time to summarize the literature on this exciting topic and provide perspectives for future research in the field.