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Angiogenesis

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28.02.2020 | Original Paper

TMEM100 is a key factor for specification of lymphatic endothelial progenitors

verfasst von: Eun-Hye Moon, Yong Hwan Kim, Phuong-Nhung Vu, Hyunjin Yoo, Kwonho Hong, Young Jae Lee, S. Paul Oh

Erschienen in: Angiogenesis | Ausgabe 3/2020

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Abstract

Background

TMEM100 is identified as a downstream gene of bone morphogenetic protein 9 (BMP9) signaling via activin receptor-like kinase 1 (ALK1), which is known to participate in lymphangiogenesis as well as angiogenesis. TMEM100 has been shown to be important for blood vessel formation and maintenance, but its role in the development of lymphatic vasculature remains unknown. The objective is to investigate the role of TMEM100 in development of the lymphatic system.

Methods and results

Global Tmem100 gene deletion was induced by tamoxifen on 10.5 days post-coitus. Tmem100-inducible knockout (iKO) embryos in embryonic days (E)14.5–16.5 exhibited edema and blood-filled enlarged lymphatics with misconnections between veins and lymphatic vessels. For a reciprocal approach, we have generated a novel mouse line in which TMEM100 overexpression (OE) can be induced in endothelial cells by intercrossing with Tie2-Cre driver. TMEM100-OE embryos at E12.5–14.5 exhibited edema with small size and number of lymphatic vessels, the exact opposite phenotypes of Tmem100-iKOs. In Tmem100-iKO embryos, the number of progenitors of lymphatic endothelial cells (LECs) in the cardinal vein was increased, while it was decreased in TMEM100-OE embryos. The activity of NOTCH signaling, which limits the number of progenitors of LECs in the cardinal vein, was decreased in Tmem100-iKO embryos, whereas it was increased in TMEM100-OE embryos.

Conclusion

TMEM100 plays an important role in the specification of LECs in the cardinal veins, at least in part, by regulating the NOTCH signaling.

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Titel: TMEM100 is a key factor for specification of lymphatic endothelial progenitors
verfasst von: Eun-Hye Moon
Yong Hwan Kim
Phuong-Nhung Vu
Hyunjin Yoo
Kwonho Hong
Young Jae Lee
S. Paul Oh
Publikationsdatum: 28.02.2020
Verlag: Springer Netherlands
Erschienen in: Angiogenesis / Ausgabe 3/2020
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-020-09713-1

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