mafba and mafbb differentially regulate lymphatic endothelial cell migration in topographically distinct manners
mafba and mafbb differentially regulate lymphatic endothelial cell migration in topographically distinct manners
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DOI：
10.1016/j.celrep.2022.110982
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发表时间：
2022-06-21
期刊：
影响因子：
8.8
通讯作者：
Koltowska, Katarzyna
中科院分区：
文献类型：
--
作者：
Arnold, Hannah;Panara, Virginia;Koltowska, Katarzyna
淋巴管生成，即从原有的血管形成淋巴管，是一个需要细胞迁移的动态过程。无论在哪里，迁徙的淋巴管内皮细胞(LEC)祖细胞都会探测周围环境以形成淋巴管网络。淋巴发育的调节需要不同物种中的转录因子MAFB。斑马鱼Mafba在LEC祖细胞中表达，是它们在躯干迁移所必需的。然而，协调LEC在不同淋巴管内皮细胞床中迁移的转录机制仍然不清楚。在这里，我们揭示了两个Paralog，Mafba和Mafbb对LEC迁移的不同地形要求。Mafba和mafbb对于面部淋巴发育都是必需的，但mafbb对于躯干淋巴发育是必不可少的。在分子水平上，我们证明了一个调控网络，其中VEGFC-Vegfd-SoxF-Mafba-Mafbb在面部淋巴管生成中是必不可少的。我们发现mafba和mafbb调节淋巴功能所必需的LEC迁移和血管形态发生的方向性。
Lymphangiogenesis, formation of lymphatic vessels from pre-existing vessels, is a dynamic process that requires cell migration. Regardless of location, migrating lymphatic endothelial cell (LEC) progenitors probe their surroundings to form the lymphatic network. Lymphatic-development regulation requires the transcription factor MAFB in different species. Zebrafish Mafba, expressed in LEC progenitors, is essential for their migration in the trunk. However, the transcriptional mechanism that orchestrates LEC migration in different lymphatic endothelial beds remains elusive. Here, we uncover topographically different requirements of the two paralogs, Mafba and Mafbb, for LEC migration. Both mafba and mafbb are necessary for facial lymphatic development, but mafbb is dispensable for trunk lymphatic development. On the molecular level, we demonstrate a regulatory network where Vegfc-Vegfd-SoxF-Mafba-Mafbb is essential in facial lymphangiogenesis. We identify that mafba and mafbb tune the directionality of LEC migration and vessel morphogenesis that is ultimately necessary for lymphatic function.