Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Dev Biol. 2012 Apr 15;364(2):89-98. doi: 10.1016/j.ydbio.2011.12.032. Epub 2011 Dec 29.
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.
在哺乳动物胚胎的淋巴管生成过程中，心静脉中的一部分血管内皮细胞被重新编程为淋巴管内皮细胞命运。淋巴管生成的主流模型认为，这些淋巴管前体细胞从心静脉迁移并重新组装成淋巴管囊，从那里生成淋巴管脉管系统。然而，该模型无法解释许多观察结果，因此这些观察结果仍然是轶事性的。在这里，我们使用光学投影断层扫描、共聚焦显微镜和体内活体成像，以高分辨率揭示了小鼠胚胎中淋巴管血管形态发生的三个关键阶段。首先，我们定义了沿心静脉前-后轴的 Prox1 阳性淋巴管内皮祖细胞的“前淋巴管簇”或“前淋巴管簇”。其次，这些前淋巴管簇经历渐进性挤出（“气球样变”）以产生原始的淋巴管囊。第三，淋巴管通过多种机制出现，包括从淋巴管囊发芽和从心静脉直接分层的细胞流。我们的数据支持淋巴管脉管系统模式和形态发生的新模型，作为识别控制这些过程的分子线索的基础。
