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Generation of First Heart Field-like Cardiac Progenitors and Ventricular-like Cardiomyocytes from Human Pluripotent Stem Cells
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Inositol 1,4,5-trisphosphate receptors are essential for the development of the second heart field

Maki Nakazawa1, Keiko Uchida, Megumi Aramaki

  • 1Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Journal of Molecular and Cellular Cardiology
|March 9, 2011
PubMed

Insights

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are crucial for second heart field (SHF) development. Mice lacking IP3R1 and IP3R3 show outflow tract defects, indicating their role in congenital heart defect (CHD) etiology.

Area of Science:

  • Developmental biology
  • Cardiovascular research
  • Molecular genetics

Background:

  • Congenital heart defects (CHDs) affect 0.5-1% of newborns, with unknown genetic causes.
  • The second heart field (SHF) is a critical source of myocardial cells for heart development.
  • Intracellular calcium (Ca2+) signaling is vital for heart development, but its role in the SHF is unclear.

Purpose of the Study:

  • To investigate the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) in SHF development.
  • To determine the contribution of IP3R-mediated Ca2+ signaling to congenital heart defect (CHD) etiology.

Main Methods:

  • Analysis of mice deficient for IP3R type 1 and type 3 (IP3R1(-/-)IP3R3(-/-)).
  • Assessment of embryonic heart development, including outflow tract and right ventricle morphology.
  • Gene expression analysis to identify affected molecular pathways.

Main Results:

  • IP3R1(-/-)IP3R3(-/-) mouse embryos exhibited outflow tract and right ventricle hypoplasia.
  • Reduced expression of SHF molecular markers and increased apoptosis in SHF mesodermal cells were observed.
  • IP3R-mediated Ca2+ signaling appears to involve the Mef2C-Smyd1 pathway in SHF development.

Conclusions:

  • IP3R type 1 and type 3 play a redundant role in the development of the second heart field (SHF).
  • IP3R-mediated Ca2+ signaling is essential for proper SHF development and may contribute to congenital heart defect (CHD) pathogenesis.

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