Multiple mouse models of primary lymphedema exhibit distinct defects in lymphovenous valve development
Multiple mouse models of primary lymphedema exhibit distinct defects in lymphovenous valve development
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DOI：
10.1016/j.ydbio.2015.10.022
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发表时间：
2016-01-01
影响因子：
2.7
通讯作者：
Srinivasan, R. Sathish
中科院分区：
文献类型：
--
作者：
Geng, Xin;Cha, Boksik;Srinivasan, R. Sathish
淋巴仅通过四个淋巴静脉瓣膜 (LVV) 返回血液循环。尽管 LVV 至关重要，但人们对其架构和开发却知之甚少。我们分析了小鼠胚胎发生过程中 LVV 的分子和超微结构水平的形成，并确定了三个关键步骤。首先，LW形成内皮细胞（LW-EC）从PROX1（+）祖细胞分化并从静脉的管腔侧分层。其次，LW-EC 聚集，垂直于淋巴流动方向排列并建立淋巴静脉连接。最后，随着壁细胞的募集，LVV 成熟。在四种不同的原发性淋巴水肿小鼠模型中，LW 形态发生受到破坏，并且 LW 缺陷的严重程度与淋巴水肿的严重程度相关。总而言之，我们提供了第一个也是最全面的 LW 发展分析。此外，我们的工作表明异常的 LVV 会导致淋巴水肿。 (C) 2015 年作者。由爱思唯尔公司出版
Lymph is returned to the blood circulation exclusively via four lymphovenous valves (LVVs). Despite their vital importance, the architecture and development of LVVs is poorly understood. We analyzed the formation of LVVs at the molecular and ultrastructural levels during mouse embryogenesis and identified three critical steps. First, LW-forming endothelial cells (LW-ECs) differentiate from PROX1(+) progenitors and delaminate from the luminal side of the veins. Second, LW-ECs aggregate, align perpendicular to the direction of lymph flow and establish lympho-venous connections. Finally, LVVs mature with the recruitment of mural cells. LW morphogenesis is disrupted in four different mouse models of primary lymphedema and the severity of LW defects correlate with that of lymphedema. In summary, we have provided the first and the most comprehensive analysis of LW development. Furthermore, our work suggests that aberrant LVVs contribute to lymphedema. (C) 2015 The Authors. Published by Elsevier Inc.