Mechanistic study of transcription factor Sox18 during heart development

Jianxin Liang, Imtiaz Ul Hassan, Man Yee Cheung, Lei Feng, Yi-jyun Lin, Qi Long, Chengdong Wang, Yuyue Ding, Ziqing Wang, Yuan Zhang, Yulong Li, Donghao Guo, Xiaofang Guo, Thomas Chi Bun Wong, Muhammad Kaleem Samma, Zixin Rong, Xufeng Qi, Dongqing Cai, Sai-Ming Ngai, Hui Zhao*

*Corresponding author for this work

    Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

    1 Citation (Scopus)

    Abstract

    Heart development is a delicate and complex process regulated by coordination of various signaling pathways. In this study, we investigated the role of sox18 in heart development by modulating Wnt/β-Catenin signaling pathways. Our spatiotemporal expression analysis revealed that sox18 is mainly expressed in the heart, branchial arch, pharyngeal arch, spinal cord, and intersegmental vessels at the tailbud stage of Xenopus tropicalis embryo. Overexpression of sox18 in the X. tropicalis embryos causes heart edema, while loss-of-function of sox18 can change the signal of developmental heart marker gata4 at different stages, suggesting that sox18 plays an essential role in the development of the heart. Knockdown of SOX18 in human umbilical vein endothelial cells suggests a link between Sox18 and β-CATENIN, a key regulator of the Wnt signaling pathway. Sox18 negatively regulates islet1 and tbx3, the downstream factors of Wnt/β-Catenin signaling, during the linear heart tube formation and the heart looping stage. Taken together, our findings highlight the crucial role of Sox18 in the development of the heart via inhibiting Wnt/β-Catenin signaling. © 2024 Elsevier Inc.
    Original languageEnglish
    Article number114472
    JournalGeneral and Comparative Endocrinology
    Volume350
    Online published17 Feb 2024
    DOIs
    Publication statusPublished - 1 May 2024

    Funding

    This work was supported by the National Key R&D Program of China, Grant/Award Number: 2016YFE0204700 , the Research Grants Council of Hong Kong (14112618 and 14119120) to HZ, and CRF equipment grant C5033-19E. Additional support was provided by the Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics to HZ (8601012). We thank our laboratory colleagues for their helpful discussion in this project.

    Research Keywords

    • Heart development
    • Sox18
    • Transcriptional factor
    • Wnt signaling pathway
    • Xenopus

    RGC Funding Information

    • RGC-funded

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