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Research of extracellular matrix in the morphogenesis of tracnsposition of the great arteries

Research Project

Project/Area Number 07671281
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionTokyo Women's Medical College

Principal Investigator

YASUI Hiroshi  Tokyo Women's Medical College, Department of Medicine, assistant, 医学部, 助手 (60210241)

Co-Investigator(Kenkyū-buntansha) TOMITA Sachiko  Tokyo Women's Medical College, Department of Medicine, assistant, 医学部, 助手 (40231451)
MORISHIMA Masae  Tokyo Women's Medical College, Department of Medicine, assistant, 医学部, 助手 (00241068)
NAKAZAWA Makoto  Tokyo Women's Medical College, Department of Medicine, professor, 医学部, 教授 (10075567)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordscardiac development / extracellular matrix / mouse / retinoic acid / integrin / インデグリン / 形態形成 / 大血管転換症
Research Abstract

First, we analized the morphogenetic process of the mouse model of transposition of the great arteries. We found that a pair of conus swellings, consisted of extracellular matrix, was hypoplastic and dysplatic before outflfow septum formation and that the outflow swellings lacked counterclockwise rotationand geve rise to straight outflow septum. Second, we looked at the localization of extracellular matrix along cardiac outflow tract destined to develop transposition and found that collagen type I,fibronectin and hyaluronaic acid distributed differently from the control. Then we looked at the immunohistochemical distribution of integrin alpha 4 which is a receptor of fibronectin. In the gestation day 10-12 mouse embryos, integrin alpha 4 was found at the endocardium-derived mesenchymes in the cardiac inflow and outflow tract, neural crest-derived outflow septeum, sinus venosus septum and left Cuvier's duct in accordance with the distribution of fibronectin, suggesting the active role role of integrin alpha 4 in the cardiac morphogenesis. However, integrin alpha 4 did not appear to be involved in the induction of hypoplasia of the cardiac jelly at gestation day 9. Receptors of collagen type I and/or hyaluronic acid might be associated with the process, however, this possibility is currently under investigation. On the other hand, by injecting retinoic acid two days earlier, complex heart defects associated with abnormality of leftright sidedness, i.e., viscero-atrial heteriraxy, are induced. Transposition of the great arteries appears among the heart defects. Less dose of rertinoic acid can induce the conotruncal anomalies with normal relation of the great arteries, which form a spectrum of vonotruncal anomalies includes transposition of great arteries. We plan to investigate the abnormality of ectracellular matrices, their receptors and their signal transduction pathways in those extended model of transposition.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report

URL: 

Published: 1995-04-01   Modified: 2016-04-21  

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