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Updated: May 15, 2025

En Face Endocardial Cushion Preparation for Planar Morphogenesis Analysis in Mouse Embryos
Published on: July 27, 2022
GPAT4 sustains endoplasmic reticulum homeostasis in endocardial cells and safeguards heart development
Tianyang Zhao1, Kuipei Jin2,3, Xiaodong Wang1
1State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, and Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing, China.
Abstract:
The endocardium plays a pivotal role in governing myocardial development, and understanding the intrinsic regulatory insights will help apprehend pathological cardiomyopathy. Glycerol-3-phosphate acyltransferase 4 (GPAT4) is an endoplasmic reticulum (ER) membrane anchored protein. While the role of GPAT4 in glycerophospholipid biosynthesis is well established, its function in the ER is less explored. Here, we generate Gpat4 global and tissue-specific knockout mice and identify the essential role of GPAT4 in endocardial development. Deficiency of GPAT4 provokes endocardial ER stress response and enhances ER-mitochondrial (ER-mito) communications, leading to mitochondrial DNA (mtDNA) escape. As a result, the cGAS-STING pathway is triggered to stimulate type-I-interferon response, which affects heart development. Finally, abolishment of the cGAS-STING-type-I-interferon pathway rescues the heart defects of Gpat4 deletion mice. These findings uncover the pivotal role of GPAT4 in the maintenance of ER homeostasis during endocardial and heart development. Meanwhile, this study highlights the importance of the cGAS-STING pathway in cardiac organogenesis.
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