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2005 Fiscal Year Final Research Report Summary

The role of semaphorin in cardiac morphogenesis

Research Project

Project/Area Number 16590682
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionOsaka University

Principal Investigator

TOYOFUKU Toshihiko  Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (60322179)

Project Period (FY) 2004 – 2005
KeywordsSema6D / Plexin-A1 / Two-hybrid system / Cardiovascular development
Research Abstract

1)Identification of signaling molecules in the Sema6D-Plexin-A1 pathway
To identify the molecules involving in the Sema6D-Plexin-A1 pathway, yeast two-hybrid system will be performed. The binding molecules are screened in the brain cDNA libraries by using the cytoplasmic region of Plexin-A1 as the bait. From 10X10^6 clones, FERM domain containing guanosine-exchange factor for Rac, named FARP2, is identified to bind to the Plexin-A1.
2)Functional analysis of FARP2
Immunoprecipitaion-immunoblot assay shows that FARP2 binds to Plexin-A1 through its FERM domain. This interaction is dependent on the presence of co-receptor Neuropilin-1. When Sema3A, one of the ligand for Plexin-A1-Neuropilin-1 receptor complex, binds to receptor complex, FARP2 is dissociates from Plexin-A1, and the released form activates its Rac GEF activity. The activation of Rac induces the sequential steps of signaling pathway to change the cytoskeletal architecture.
3)In vivo analysis of Sema6D function
(a)generation of Sema6D knockout mice and Plexin-A1 knockout mice
Construction of target vectors : Genomic DNA surrounding Sema6D or Plexin-A1 gene are isolated by the PCR and these fragments are inserted into the pNT1.1 vector. The vectors are electroporated into the mouse ES cells, and the ES cells containing the recombinant vector are selected.

  • Research Products

    (2 results)

All 2005

All Journal Article (2 results)

  • [Journal Article] FARP2 triggers signals for Sema3A-mediated axonal repulsion2005

    • Author(s)
      Toyofuku, T. et al.
    • Journal Title

      Nature Neuroscience 8

      Pages: 1712-1719

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] FARP2 triggers signals for Sema3A-mediated axonal repulsion2005

    • Author(s)
      Toyofuku, T, et al.
    • Journal Title

      Nature Neuroscience 8

      Pages: 1712-1719

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2007-12-13  

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