@article{d38e07f42b0d432a981e130658f0c407,
title = "Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling",
abstract = "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.",
author = "Kei Sugihara and Koichi Nishiyama and Shigetomo Fukuhara and Akiyoshi Uemura and Satoshi Arima and Ryo Kobayashi and Alvaro K{\"o}hn-Luque and Naoki Mochizuki and Toshio Suda and Hisao Ogawa and Hiroki Kurihara",
note = "Funding Information: We thank Dr. Takashi Miura for the modeling studies. We also thank Yuriko Kondo and Akira Matsubara for excellent technical assistance. MTrackJ was developed at the Biomedical Imaging Group Rotterdam of the Erasmus MC University Medical Center Rotterdam by Erik Meijering. This work was supported in part by the Global COE Program (Integrative Life Science based on the Study of Biosignaling Mechanisms) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) ; Platform for Dynamic Approaches to Living System from MEXT ; CREST from the JST ; grants-in-aid for scientific research from MEXT ( 23111505 and 25111705 to K.N. and 24249047 to H.K.); a grants-in-aid for scientific research from the Japan Society for the Promotion of Science (JSPS, 23591099 to K.N.); The Tokyo Society of Medical Sciences (to K.N.); the Takeda Science Foundation (to K.N.); The Shimabara Science Promotion Foundation (to K.N.); the SENSHIN Medical Research Foundation (to K.N.); and the Astellas Foundation for Research on Metabolic Disorders (to K.N.). Publisher Copyright: {\textcopyright} 2015 The Authors.",
year = "2015",
month = dec,
day = "1",
doi = "10.1016/j.celrep.2015.10.051",
language = "English",
volume = "13",
pages = "1814--1827",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",
}