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Notch signaling functions in lymphatic valve formation.
Aino Murtomaki1, Minji K Uh2, Chris Kitajewski3
1Department of OB/GYN, Columbia University Medical Center, New York, NY 10032, USA Division of Genetics, Department of Biosciences, Viikki Biocenter, University of Helsinki, POB 56, Helsinki FIN-00014, Finland.
Development (Cambridge, England)
|June 12, 2014
Summary
Notch signaling is crucial for lymphatic valve formation, regulating key proteins like integrin α9 and fibronectin EIIIA during development. This study reveals Notch
Area of Science:
- Developmental Biology
- Vascular Biology
- Cell Signaling
Background:
- Collecting lymphatic ducts possess intraluminal valves essential for preventing lymph backflow.
- Lymphatic valve morphogenesis in mice initiates around embryonic day 15.5 (E15.5).
- Prox1 expression patterns differentiate valve-forming cells from ductal cells.
Purpose of the Study:
- To investigate the role of Notch signaling in lymphatic valve morphogenesis.
- To determine how Notch signaling affects key molecular markers during valve development.
Main Methods:
- Utilized conditional lymphatic endothelial cell drivers in mice to manipulate Notch1.
- Employed a Notch reporter mouse to track Notch activity during valve development.
- Assessed the impact of Notch1 deletion and dominant-negative Mastermind-like (DNMAML) expression on cellular and molecular markers.
Main Results:
- Notch1 deletion caused Prox1(high) cell expansion, impaired reorientation, and reduced integrin α9 expression.
- DNMAML expression led to fewer valves, failed Prox1(high) cell clustering, and altered cell morphology.
- Notch signaling activation in human cells upregulated integrin α9, fibronectin EIIIA, and Cx37.
Conclusions:
- Notch signaling is indispensable for proper lymphatic valve formation.
- Notch signaling regulates critical proteins, including integrin α9 and fibronectin EIIIA, during valve morphogenesis.
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