期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41467-020-20156-6
关键词
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资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [22122002, 25713059, 15K15089, 18H05042, 18K19553, 17K15625, 18K16997, 18H02938, 18K19619, 19K07389]
- AMED-PRIME [JP19gm6210017h0001, JP20gm6210017h0002]
- Inamori Foundation
- Kao Foundation for Arts and Culture
- Takeda Science Foundation
- Mochida Memorial Foundation
- Mitsubishi Foundation
- Cell Science Research Foundation
- SENSHIN Medical Research Foundation
- Sumitomo Foundation
- Daiichi Sankyo Foundation of Life Science
- Naito Foundation
- Uehara Memorial Foundation
- Joint Usage/Research Center Program of the Advanced Medical Research Center, Yokohama City University
- Toray Science Foundation
- Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research
- Grants-in-Aid for Scientific Research [19K07389, 18H02938, 18H05042, 18K19619, 18K16997, 15K15089, 22122002, 17K15625, 18K19553] Funding Source: KAKEN
Blood and lymphatic vessels structurally bear a strong resemblance but never share a lumen, thus maintaining their distinct functions. Although lymphatic vessels initially arise from embryonic veins, the molecular mechanism that maintains separation of these two systems has not been elucidated. Here, we show that genetic deficiency of Folliculin, a tumor suppressor, leads to misconnection of blood and lymphatic vessels in mice and humans. Absence of Folliculin results in the appearance of lymphatic-biased venous endothelial cells caused by ectopic expression of Prox1, a master transcription factor for lymphatic specification. Mechanistically, this phenotype is ascribed to nuclear translocation of the basic helix-loop-helix transcription factor Transcription Factor E3 (TFE3), binding to a regulatory element of Prox1, thereby enhancing its venous expression. Overall, these data demonstrate that Folliculin acts as a gatekeeper that maintains separation of blood and lymphatic vessels by limiting the plasticity of committed endothelial cells. Blood and lymphatic vessels bear a strong resemblance but do not share a lumen, thus maintaining their distinct functions. Here, the authors describe that Folliculin, a tumor suppressor, prevents the fusion of these vessels during development by limiting the plasticity of venous and lymphatic endothelial cells.
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