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. 2025 Feb;46(2):404-415.
doi: 10.1038/s41401-024-01392-8. Epub 2024 Sep 23.

Adaptor protein Src-homology 2 domain containing E (SH2E) deficiency induces heart defect in zebrafish

Yu-Lai Liang #  1   2 , Yang-Xi Hu #  3   4 , Fang-Fang Li #  5 , Hong-Min You  6 , Jian Chen  2 , Chun Liang  3 , Zhi-Fu Guo  6 , Qing Jing  7
Affiliations

Adaptor protein Src-homology 2 domain containing E (SH2E) deficiency induces heart defect in zebrafish

Yu-Lai Liang et al. Acta Pharmacol Sin. 2025 Feb.

Abstract

Adaptor proteins play crucial roles in signal transduction across diverse signaling pathways. Src-homology 2 domain-containing E (SH2E) is the adaptor protein highly expressed in vascular endothelial cells and myocardium during zebrafish embryogenesis. In this study we investigated the function and mechanisms of SH2E in cardiogenesis. We first analyzed the spatiotemporal expression of SH2E and then constructed zebrafish lines with SH2E deficiency using the CRISPR-Cas9 system. We showed that homozygous mutants developed progressive pericardial edema (PCE), dilated atrium, abnormal atrioventricular looping and thickened atrioventricular wall from 3 days post fertilization (dpf) until death; inducible overexpression of SH2E was able to partially rescue the PCE phenotype. Using transcriptome sequencing analysis, we demonstrated that the MAPK/ERK and NF-κB signaling pathways might be involved in SH2E-deficiency-caused PCE. This study underscores the pivotal role of SH2E in cardiogenesis, and might help to identify innovative diagnostic techniques and therapeutic strategies for congenital heart disease.

Keywords: CRISPR/Cas9; Src-homology 2 domain containing E; cardiac development; pericardial edema; zebrafish.

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Conflict of interest statement

Competing interests: The authors declare no conflict of interest. Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences has applied for a patent, China Patent Application No. 202311014379.7 by inventors Qing Jing, Yang-xi Hu, Yu-lai Liang and Zhi-hua Liu for the usage of L-selenomethionine in antioxidant stress and alleviation of cardiac developmental defects caused by SH2E gene mutations described in this paper under the support of the Program of EnShi TuJia and Miao Autonomous Prefecture Bureau of Scientific and Technological Affairs.

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