Mechanisms regulating heart mesoderm formation

• Project/Area Number: 17590169
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Osaka City University
• Principal Investigator: NAKAJIMA Yuji Osaka City University, Graduate School of Medicine, Professor (80207795)
• Co-Investigator(Kenkyū-buntansha): IKEDA Kazuo Osaka City University, Graduate School of Medicine, Associate Professor (80275247) ; NAKATANI Kazuki Osaka City University, Graduate School of Medicine, Lecturer (60295699)
• Project Period (FY): 2005 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: Anatomical Science / Development / Regeneration Medicine / Heart / Cardiomyocyte / Heart mesoderm

Research Abstract

During heart development at the gastrula stage, inhibition of BMP activity affects the heart specification but does not impair the expression of smooth muscle alpha-actin (SMA), which is first expressed in the heart mesoderm and recruited into initial heart myofibrils. Interaction of tissues between posterior epiblast and hypoblast at the early blastula stage is necessary to induce the expression of SMA, in which Nodal and Chordin are thought to be involved. Here we investigated the role of FGF8 in the expression of SMA. In situ hybridization and RT-PCR showed that Fgf8b is expressed predominantly in the nascent hypoblast. Anti-FGF8b antibody inhibited the expression of SMA, cTNT, and Tbx5, which are BMP-independent heart mesoderm/early cardiomyocyte genes, but not Brachyury in cultured posterior blastoderm, and combined FGF8b and Nodal, but neither factor alone induced the expression of SMA in association with heart specific markers in cultured epiblast. Although FGF8b did not induce the upregulation of phospho-Smad2, anti-FGF8b properties suppressed phospho-Smad2 in cultured blastoderm. FGF8b was able to reverse the BMP-induced inhibition of cardiomyogenesis. The results suggest that FGF8b acts on the epiblast synergistically with Nodal at the pregastrula stage and may play a role in the expression of SMA during early cardiogenesis.

Research Products

• [Journal Article] Induction of initial heart α-actin,smooth muscle α-actin,in chick pregastrula epiblastlThe role of hypoblast and fibroblast growth factor-8. (2008)
  • Author(s): Matsui H, Sakabe M, Sakata H, Yanagawa N, Ikeda K, Yamagishi T, Nakajima Y.
  • Journal Title: Develop Growth Differ 50 Pages: 143-157
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Induction of initial heart α-actin, smooth muscle a-actin, in chick pregastrula epiblast: The role of hypoblast and fibroblast growth factor-8 (2008)
  • Author(s): Matsui, H., Sakabe, M., Sakata, H., Yanagawa, N., Ikeda, K., Yamagishi, T., Nakajima Y
  • Journal Title: Develop Growth Differ 50 Pages: 143-157
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Induction of initial heart α-actin,smooth muscle α-actin,in chick pregastrula epiblast:The role of hypoblast and fibroblast growth factor-8. (2008)
  • Author(s): Matsui H, Sakabe M, Sakata H, Yanagawa N, Ikeda K, Yamagishi T, Nakajima Y.
  • Journal Title: Development Growth Differentiation 50 Pages: 143-157
  • Peer Reviewed
• [Journal Article] Rho Kinase inhibitor Y27632 affects initial heart myofibrillogenesis incultured chick blastoderm. (2007)
  • Author(s): Sakata H, Sakabe M, Matsui H, Kawada N, Nakatani K, Ikeda K, Yamagishi T, Nakajima Y
  • Journal Title: Dev Dyn 236 Pages: 461-472
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Rho Kinase inhibitor Y27632 affects initial heart myofibrillogenesis in cultured chick blastoderm (2007)
  • Author(s): Sakata, H., Sakabe, M., Matsui, H., Kawada, N., Nakatani, K., Ikeda, K., Yamagishi, T., Nakajima, Y
  • Journal Title: Dev Dyn 236 Pages: 461-472
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Induction of smooth muscle a-actin positive heart mesoderm is regulated by combined Nodal and FGF8 function in avian pregastrula epiblast (2007)
  • Author(s): Matsui, H., Sakabe, M., Sakata, H., Ikeda, K., Yamagishi, T., Nakajima, Y
  • Journal Title: In Future Aspects of Medical Sciences and Education. Challenge of Integrated Medical Sciences. Nadal-Ginard B and Takakura K (ed) IREIIMS, Tokyo(ISBN978-4-86281-002-1 C3047) Pages: 20-23
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Rho Kinase inhibitor Y27632 affects initial heart myofibrillogenesis in cultured chick blastoderm. (2007)
  • Author(s): Sakata H, Sakabe M, Matsui H, Kawada N, Nakatani K, Ikeda K, Yamagishi T, Nakajima Y
  • Journal Title: Developmental Dynamics 236 Pages: 461-472
• [Journal Article] Heart Myofibrillogenesis occurs in isolated chick posterior blastoderm:a culture model. (2006)
  • Author(s): Matsui H, Sakabe M, Sakata H, Nakatani K, Ikeda K, Fukui M, Ando K, Yamagishi T, Nakajima Y.
  • Journal Title: Acta Histochem Cytochem 39 Pages: 94-104
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Heart Myofibrillogenesis occurs in isolated chick posterior blastoderm: a culture model (2006)
  • Author(s): Matsui, H., Sakabe, M., Sakata, H., Nakatani, K., Ikeda, K., Fukui, M., Ando, K., Yamagishi, T.,Nakajima, Y
  • Journal Title: Acta Histochem Cytochem 39 Pages: 139-144
  • NAID: 110006203402
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Heart Myofibrilogenesis occurs in isolated chick posterior blastoderm : a culture model. (2006)
  • Author(s): Matsui H, Sakabe M, Sakata H, Nakatani K, Ikeda K, Fukui M, Ando K, Yamagishi T, Nakajima Y
  • Journal Title: Acta Histochem Cytochem 39 Pages: 139-144
• [Journal Article] Rho kinases regulate endothelial invasion and migration during valvuloseptal endocardial cushion tissue formation. (2006)
  • Author(s): Sakabe M, Ikeda K, Nakatani K, Kawada N, Imanaka-Y K, Yoshida T, Yamagishi T, Nakajima Y.
  • Journal Title: Developmental Dynamics 235 Pages: 94-104
• [Journal Article] Induction of initial cardiomyocyte α-Actin - smooth muscle □-actin - in cultured avian pregastrula epiblast : a role for nodal and BMP antagonist. (2005)
  • Author(s): Matsui H, Ikeda K, Nakatani K, Sakabe M, Yamagishi T, Nakanishi T, Nakajima Y.
  • Journal Title: Developmental Dynamics 233 Pages: 1419-1429
• [Journal Article] Understanding heart development and congenital heart defects through developmental biology: A segmental approach. (2005)
  • Author(s): Sakabe M, Matsui H, Sakata H, Ando K, Yamagishi T, Nakajima Y.
  • Journal Title: Congenital Anomalies 45 Pages: 107-118
  • NAID: 10027384326
• [Presentation] ROCK1 expression is regulated by TGFb3 and ALK2 during valvuloseptal endocardial cushion formation. (2007)
  • Author(s): Sakabe S, Sakata H, Matsui H, Ikeda K, Yamagishi T, Nakajima Y.
  • Organizer: The American Society for Cell Biology, 47th Annual Meeting
  • Place of Presentation: Washington DC.
• [Presentation] Induction of heart mesoderm is regulated by combined Nodal and FGF8b function in cultured pregastrula epiblast. (2006)
  • Author(s): Matsui H, Sakabe M, Sakata H, Kazuo K, Yamagishi T, Nakajima Y.
  • Organizer: 2nd IREIIMS(International Research and Education Institute for Integrated Medical Sciences)Open Symposium
  • Place of Presentation: Tokyo
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Induction of heart mesoderm is regulated by combined Nodal and FGF8b funotion in cultured pregastrula epiblast. (2006)
  • Author(s): Matsui, H., Sakabe, M., Sakata, H., Kazuo K., Yamagishi, T., Nakajima, Y
  • Organizer: 2nd IREIIMS (International Research and Education Institute for Integrated Medical Sciences) Open Symposium
  • Place of Presentation: Tokyo
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] In Future Aspects of Medical Sciences and Education.Challenge of Integrated Medical Sciences. (2007)
  • Author(s): Matsui H, Sakabe M, Sakata H, Ikeda K, Yamagishi T, Nakajima Y.
  • Total Pages: 4
  • Publisher: IREIIMS,Tokyo(ISBN978-4-86281-002-1 C3047)
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Aspects of Medical Sciences and Education.Challenge of Integrated Medical Sciences. (2007)
  • Author(s): Matsui H, Sakabe M, Sakata H, Ikeda K, Yamagishi T, Nakajima Y.
  • Total Pages: 193
  • Publisher: IREIIMS(ISBN978-4-86281-002-1 C3047)