血管发育的最新进展。
Recent advances in vascular development.
机构信息
Department of Molecular, Cell and Developmental Biology and Molecular Biology Institute, University of California, Los Angeles, California, USA.
出版信息
Curr Opin Hematol. 2012 May;19(3):176-83. doi: 10.1097/MOH.0b013e3283523e90.
PURPOSE OF REVIEW
This review offers a concise summary of the most recent experimental advances in vascular development using the mouse as a model organism.
RECENT FINDINGS
Recent mouse studies have revealed a spread of phenotypic diversity between endothelia of distinct developmental origins and organs. For example, expression of unique transcription factors distinguishes hemogenic from nonhemogenic endothelium within the same vessel. Vasculature of the brain is particularly susceptible to endothelial malformations due to combinatorial germline and somatic mutations; surprisingly these mutations can afflict the endothelium by either cell autonomous or paracrine effects. Mutant mice have been used to understand how multiple signaling pathways integrate and refine cellular responses. In particular, we learned how VEGFR3 regulates Notch signaling and EphrinB2 coordinates VEGFR2 responses. The regulation of Prox1 by miR181 highlighted the contribution of microRNAs in the induction of lymphatic endothelium. Information gained on heterotypic interactions has further clarified the influence of blood vessels on the morphogenesis of parenchyma and contributed to our understanding of organ-specific endothelial differentiation. Finally, mouse models have uncovered endothelial cell polarity as a keystone for successful vascular lumenization.
SUMMARY
Our understanding of the process of vascular development has gained significant refinement in the last two years and has clarified the origin of several disorders rooted in development.
目的综述
本文对以小鼠为模式生物的血管发育最新实验进展进行了简明总结。
最近的发现
最近的小鼠研究揭示了不同发育起源和器官的内皮细胞之间表型多样性的扩散。例如，独特转录因子的表达将同一血管中的造血内皮与非造血内皮区分开来。由于组合的种系和体细胞突变，脑血管特别容易发生内皮畸形；令人惊讶的是，这些突变可以通过细胞自主或旁分泌作用影响内皮细胞。突变小鼠被用于理解多种信号通路如何整合和细化细胞反应。特别是，我们了解了 VEGFR3 如何调节 Notch 信号以及 EphrinB2 如何协调 VEGFR2 反应。miR181 对 Prox1 的调控强调了 microRNAs 在诱导淋巴管内皮中的作用。关于异型相互作用的信息进一步阐明了血管对实质形态发生的影响，并有助于我们理解特定于器官的内皮细胞分化。最后，小鼠模型揭示了内皮细胞极性作为血管管腔化成功的关键。
总结
在过去两年中，我们对血管发育过程的理解有了显著的细化，并澄清了几种源于发育的疾病的起源。
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