Summary of Research Project Results under JSPS FY2003
"Research for the Future Program"

1.Research Institution The University of Tokyo
2.Research Area Life Sciences
3.Research Field Angiogenesis and Vascular Development Control
4.Term of Project FY 2000 - FY 2003
5.Project Number 00L01306
6.Title of Project Mechanisms of Vascular Smooth Muscle Differentiation and Interaction between Smooth Muscle and Endothelial Cells during Vascular Formation

7.Project Leader
Name Institution,Department Title of Position
Hiroki, Kurihara The University of Tokyo, Graduate School of Medicine Professor

8.Core Members

Names Institution,Department Title of Position
Nobuyuki, Takakura Kanazawa University, Cancer Research Institute Professor

9.Summary of Research Results

   This project aimed to the clarification of mechanisms underlying smooth muscle differentiation and cell-to-cell interaction during angiogenesis. Hiroki Kurihara and his colleagues studied neural crest cell differentiation to smooth muscle cells of the great vessels and identified endothelin-1 and its downstream genes such as dHAND as key regulators of this process. They also found that transcriptional mechanism of Pax3, involved in great vessel formation, was found to involve coactivator TAZ. In researched on cell-to-cell interaction during angiogenesis, they discovered that adrenomedullin is essential for integrity of vascular structure and that ADAMTS-1 is involved in vascularization of the adrenal medulla. Nobuyuki Takakura and his colleagues discovered that hematopoietic stem cells produce angiopoietin-1 and induce angiogenesis. They also found that hematopoietic cell-derived neuropilin-1 enhances VEGF-induced angiogenesis. Furthermore, they demonstrated that constitutive activation of Tie2 results in the inhibition of angiogenesis by inducing adhesion to mural cells. On the background of these achievements, Kurihara's group embarked on a study to dissect the mechanism of cell differentiation by using nuclear transfer technique, which may give a basis for new field of regeneration medicine.

10.Key Words
(1)angiogenesis  (2)vascular endothelial cells  (3)vascular smooth muscle cells 
(4)mural cells  (5)cell differentiation  (6)morphogenesis 
(7)transcription factor  (8)cellular interaction  (9)nuclear transfer