Segmental territories along the cardinal veins generate lymph sacs via a ballooning mechanism during embryonic lymphangiogenesis in mice
Segmental territories along the cardinal veins generate lymph sacs via a ballooning mechanism during embryonic lymphangiogenesis in mice
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DOI：
10.1016/j.ydbio.2011.12.032
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发表时间：
2012-04-15
影响因子：
2.7
通讯作者：
Koopman, Peter
中科院分区：
文献类型：
--
作者：
Francois, Mathias;Short, Kieran;Koopman, Peter
在哺乳动物胚胎的淋巴管生成过程中，主静脉中的血管内皮细胞亚群被重编程以采用淋巴管内皮命运。淋巴管生成的流行模型认为，这些淋巴前体细胞从主静脉迁移并在外周重新组装为淋巴囊，淋巴管系统从淋巴囊产生。然而，这一模型未能解释一些观察结果，因此，这些观察结果仍然是轶事。在这里，我们使用光学投影断层扫描，共聚焦显微镜和活体成像，以高分辨率揭示小鼠胚胎淋巴管形态发生的三个关键阶段。首先，我们定义领土或“前淋巴簇”的Prox 1阳性淋巴管内皮祖细胞沿着前后轴的主静脉。第二，这些前淋巴簇经历进行性挤出（“气球样变”）以产生原始淋巴囊。第三，淋巴管通过多种机制的组合出现，包括从淋巴囊发芽和从主静脉直接分层的细胞流。我们的数据支持一个新的模型，淋巴管的图案和形态发生，作为一个基础，确定这些过程的分子线索。(C)2012 Elsevier Inc. All rights reserved.
During lymphangiogenesis in the mammalian embryo, a subset of vascular endothelial cells in the cardinal veins is reprogrammed to adopt a lymphatic endothelial fate. The prevailing model of lymphangiogenesis contends that these lymphatic precursor cells migrate away from the cardinal veins and reassemble peripherally as lymph sacs from which a lymphatic vasculature is generated. However, this model fails to account for a number of observations that, as a result, have remained anecdotal. Here, we use optical projection tomography, confocal microscopy and in vivo live imaging to uncover three key stages of lymphatic vascular morphogenesis in the mouse embryo at high resolution. First, we define territories or "pre-lymphatic clusters" of Prox1-positive lymphatic endothelial progenitor cells along the antero-posterior axis of the cardinal veins. Second, these pre-lymphatic clusters undergo progressive extrusion ("ballooning") to generate primitive lymph sacs. Third, lymphatic vessels emerge by a combination of mechanisms including sprouting from the lymph sacs and direct delamination of streams of cells from the cardinal veins. Our data support a new model for lymphatic vascular patterning and morphogenesis, as a basis for identifying the molecular cues governing these processes. (C) 2012 Elsevier Inc. All rights reserved.