RhoJ-mediated regulation of endothelial cell movements and vascular patterning

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293078
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Nagoya City University (2014-2015); Kobe University (2013)
• Principal Investigator: Uemura Akiyoshi 名古屋市立大学, 医学(系)研究科(研究院), 教授 (30373278)
• Co-Investigator(Renkei-kenkyūsha): FUKUSHIMA Yoko 大阪大学, 大学院医学系研究科, 助教 (70647031) ; MOCHIZUKI Naoki 独立行政法人国立循環器病研究センター, 細胞生物学部, 部長 (30311426) ; NISHIYAMA Koichi 熊本大学, 国際先端医学研究機構, 特任准教授 (80398221) ; MIURA Takashi 九州大学, 大学院医学研究院, 教授 (10324617)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: RhoJ / VEGF / Sema3E / 血管新生 / 内皮細胞 / シグナル伝達 / 網膜 / 腫瘍

Outline of Final Research Achievements

In newly formed blood vessels, migratory behaviors of angiogenic endothelial cells (ECs) are controlled by various attractive and repulsive signals, including vascular endothelial growth factor (VEGF) and semaphorin 3E (Sema3E). However, it remains unclear how individual ECs determine their migratory directions by integrating these extrinsic signals. In this research program, we discovered that a small GTPase RhoJ regulates directional EC movements by mediating intracellular signals downstream of both VEGF and Sema3E. We further identified that RhoJ modulates vascular patterning in developing retinas as well as in oxygen-induced retinopathy. Together, our present results will contribute to the understanding of molecular and cellular mechanisms underlying morphogenetic patterning, not only in vasculature but also in neural networks in which axonal guidance is cooperatively navigated by attractive and repulsive cues.

Free Research Field

血管生物医学、眼科学