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Inositol 1,4,5-trisphosphate receptor 2 as a novel marker of vasculature to delineate processes of cardiopulmonary development.

Authors :
Ishizaki-Asami, Reina
Uchida, Keiko
Tsuchihashi, Takatoshi
Shibata, Akimichi
Kodo, Kazuki
Emoto, Katsura
Mikoshiba, Katsuhiko
Takahashi, Takao
Yamagishi, Hiroyuki
Source :
Developmental Biology. Feb2020, Vol. 458 Issue 2, p237-245. 9p.
Publication Year :
2020

Abstract

Congenital heart diseases (CHDs) involving the outflow tract (OFT), such as persistent truncus arteriosus (PTA), lead to mortality and morbidity with implications not only in the heart, but also in the pulmonary vasculature. The mechanisms of pulmonary artery (PA) development and the etiologies underlying PA disorders associated with CHD remain poorly understood partly because of a specific marker for PA development is nonexistent. The three subtypes of inositol 1,4,5-trisphosphate receptors (IP 3 R1, 2, and 3) are intracellular Ca2+ channels that are essential for many tissues and organs. We discovered that IP 3 R2 was expressed in the vasculature and heart during development using transgenic mice, in which a LacZ marker gene was knocked into the IP 3 R2 locus. Whole-mount and section LacZ staining showed that IP 3 R2-LacZ-positive cells were detectable exclusively in the smooth muscle cells, or tunica media, of PA, merging into αSMA-positive cells during development. Furthermore, our analyses suggested that IP 3 R2-LacZ positive PA smooth muscle layers gradually elongate from the central PA to the peripheral PAs from E13.5 to E18.5, supporting the distal angiogenesis theory for the development of PA, whereas IP 3 R2-LacZ was rarely expressed in smooth muscle cells in the pulmonary trunk. Crossing IP 3 R-LacZ mice with mice hypomorphic for Tbx1 alleles revealed that PTA of Tbx1 mutants may result from agenesis or hypoplasia of the pulmonary trunk; thus, the left and right central to peripheral PAs connect directly to the dorsal side of the truncus arteriosus in these mutants. Additionally, we found hypercellular interstitial mesenchyme and delayed maturation of the lung endoderm in the Tbx1 mutant lungs. Our study identifies IP 3 R2 as a novel marker for clear visualization of PA during development and can be utilized for studying cardiopulmonary development and disease. • IP 3 R2-LacZ is expressed in the pulmonary artery smooth muscle cells in lungs. • IP 3 R2-LacZ is expressed in the outflow tract derived from the splanchnic mesoderm. • Formation of the pulmonary trunk was impaired in Tbx1 hypomorphic heart. • Maturation of Tbx1 hypomorphic lungs was delayed in the late stage of development. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00121606
Volume :
458
Issue :
2
Database :
Academic Search Index
Journal :
Developmental Biology
Publication Type :
Academic Journal
Accession number :
141435713
Full Text :
https://doi.org/10.1016/j.ydbio.2019.11.011