Article

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

Yu-lai Liang1,2, Yang-xi Hu3,4, Fang-fang Li5, Hong-min You6, Jian Chen2, Chun Liang3, Zhi-fu Guo6, Qing Jing2
1 Laboratory of Molecular Immunology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China
2 CAS Key Laboratory of Tissue Microenvironment and Tumor, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
3 Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
4 Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
5 Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
6 Department of Cardiovascular Medicine, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Correspondence to: Fang-fang Li: lifang091001@163.com, Qing Jing: qjing@sibs.ac.cn,
DOI: 10.1038/s41401-024-01392-8
Received: 3 May 2024
Accepted: 5 September 2024
Advance online: 23 September 2024

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

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