Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling
- Sugihara, K., Nishiyama, K., Fukuhara, S., Uemura, A., Arima, S., Kobayashi, R., Köhn-Luque, A., Mochizuki, N., Suda, T., Ogawa, H., Kurihara, H.
- Cell Reports 13: 1814-27 (Journal)
- Registered Authors
- Fukuhara, Shigetomo, Mochizuki, Naoki
- MeSH Terms
- Cell Movement/drug effects
- Embryo, Nonmammalian/metabolism
- Endothelial Cells/drug effects
- Endothelial Cells/metabolism
- Mice, Inbred C57BL
- Models, Biological*
- Neovascularization, Physiologic/drug effects
- Retina/drug effects
- Time-Lapse Imaging
- Vascular Endothelial Growth Factor A/pharmacology
- Zebrafish/growth & development
- 26655898 Full text @ Cell Rep.
Sugihara, K., Nishiyama, K., Fukuhara, S., Uemura, A., Arima, S., Kobayashi, R., Köhn-Luque, A., Mochizuki, N., Suda, T., Ogawa, H., Kurihara, H. (2015) Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling. Cell Reports. 13:1814-27.
Angiogenesis is a multicellular phenomenon driven by morphogenetic cell movements. We recently reported morphogenetic vascular endothelial cell (EC) behaviors to be dynamic and complex. However, the principal mechanisms orchestrating individual EC movements in angiogenic morphogenesis remain largely unknown. Here we present an experiment-driven mathematical model that enables us to systematically dissect cellular mechanisms in branch elongation. We found that cell-autonomous and coordinated actions governed these multicellular behaviors, and a cell-autonomous process sufficiently illustrated essential features of the morphogenetic EC dynamics at both the single-cell and cell-population levels. Through refining our model and experimental verification, we further identified a coordinated mode of tip EC behaviors regulated via a spatial relationship between tip and follower ECs, which facilitates the forward motility of tip ECs. These findings provide insights that enhance our mechanistic understanding of not only angiogenic morphogenesis, but also other types of multicellular phenomenon.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes