Blood and lymphatic systems are segregated by the FLCN tumor suppressor

Ikue Tai-Nagara, Yukiko Hasumi, Dai Kusumoto, Hisashi Hasumi, Keisuke Okabe, Tomofumi Ando, Fumio Matsuzaki, Fumiko Itoh, Hideyuki Saya, Chang Liu, Wenling Li, Yoh-suke Mukouyama, W. Marston Linehan, Xinyi Liu, Masanori Hirashima, Yutaka Suzuki, Shintaro Funasaki, Yorifumi Satou, Mitsuko Furuya, Masaya Baba () and Yoshiaki Kubota ()
Additional contact information
Ikue Tai-Nagara: Keio University School of Medicine
Yukiko Hasumi: Yokohama City University Graduate School of Medicine
Dai Kusumoto: Keio University School of Medicine
Hisashi Hasumi: National Cancer Institute, National Institutes of Health
Keisuke Okabe: Keio University School of Medicine
Tomofumi Ando: Keio University School of Medicine
Fumio Matsuzaki: RIKEN Center for Biosystems Dynamics Research
Fumiko Itoh: Tokyo University of Pharmacy and Life Sciences
Hideyuki Saya: Institute for Advanced Medical Research, Keio University School of Medicine
Chang Liu: Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health
Wenling Li: Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health
Yoh-suke Mukouyama: Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health
W. Marston Linehan: National Cancer Institute, National Institutes of Health
Xinyi Liu: Niigata University Graduate School of Medical and Dental Sciences
Masanori Hirashima: Niigata University Graduate School of Medical and Dental Sciences
Yutaka Suzuki: Graduate School of Frontier Sciences, The University of Tokyo
Shintaro Funasaki: International Research Center for Medical Sciences, Kumamoto University
Yorifumi Satou: Kumamoto and Kagoshima Universities
Mitsuko Furuya: Yokohama City University Graduate School of Medicine
Masaya Baba: National Cancer Institute, National Institutes of Health
Yoshiaki Kubota: Keio University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-20156-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20156-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-20156-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().