Inositol 1,4,5-trisphosphate receptors are essential for the development of the second heart field

Maki Nakazawa, Keiko Uchida, Megumi Aramaki, Kazuki Kodo, Chihiro Yamagishi, Takao Takahashi, Katsuhiko Mikoshiba, Hiroyuki Yamagishi

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Congenital heart defects (CHDs) occur in 0.5-1% of live births, yet the underlying genetic etiology remains mostly unknown. Recently, a new source of myocardial cells, namely the second heart field (SHF), was discovered in the splanchnic mesoderm. Abnormal development of the SHF leads to a spectrum of outflow tract defects, such as persistent truncus arteriosus and tetralogy of Fallot. Intracellular Ca 2+ signaling is known to be essential for many aspects of heart biology including heart development, but its role in the SHF is uncertain. Here, we analyzed mice deficient for genes encoding inositol 1,4,5-trisphosphate receptors (IP 3Rs), which are intracellular Ca 2+ release channels on the endo/sarcoplasmic reticulum that mediate Ca 2+ mobilization. Mouse embryos that are double mutant for IP 3R type 1 and type 3 (IP 3R1 -/-IP 3R3 -/-) show hypoplasia of the outflow tract and the right ventricle, reduced expression of specific molecular markers and enhanced apoptosis of mesodermal cells in the SHF. Gene expression analyses suggest that IP 3R-mediated Ca 2+ signaling may involve, at least in part, the Mef2C-Smyd1 pathway, a transcriptional cascade essential for the SHF. These data reveal that IP 3R type 1 and type 3 may play a redundant role in the development of the SHF.

Original languageEnglish
Pages (from-to)58-66
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume51
Issue number1
DOIs
Publication statusPublished - 2011 Jul 1

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Keywords

  • Ca channel
  • Ca signaling
  • Congenital heart defect
  • Heart development
  • Outflow tract

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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