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 language | English |
|---|---|
| Pages (from-to) | 58-66 |
| Number of pages | 9 |
| Journal | Journal of Molecular and Cellular Cardiology |
| Volume | 51 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2011 Jul |
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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
Cite this
Inositol 1,4,5-trisphosphate receptors are essential for the development of the second heart field. / Nakazawa, Maki; Uchida, Keiko; Aramaki, Megumi; Kodo, Kazuki; Yamagishi, Chihiro; Takahashi, Takao; Mikoshiba, Katsuhiko; Yamagishi, Hiroyuki.
In: Journal of Molecular and Cellular Cardiology, Vol. 51, No. 1, 07.2011, p. 58-66.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inositol 1,4,5-trisphosphate receptors are essential for the development of the second heart field
AU - Nakazawa, Maki
AU - Uchida, Keiko
AU - Aramaki, Megumi
AU - Kodo, Kazuki
AU - Yamagishi, Chihiro
AU - Takahashi, Takao
AU - Mikoshiba, Katsuhiko
AU - Yamagishi, Hiroyuki
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - Ca channel
KW - Ca signaling
KW - Congenital heart defect
KW - Heart development
KW - Outflow tract
UR - http://www.scopus.com/inward/record.url?scp=79956302999&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79956302999&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2011.02.014
DO - 10.1016/j.yjmcc.2011.02.014
M3 - Article
C2 - 21382375
AN - SCOPUS:79956302999
VL - 51
SP - 58
EP - 66
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 1
ER -