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Published August 8, 2019 | Accepted Version + Published
Journal Article Open

Cardiac neural crest contributes to cardiomyocytes in amniotes and heart regeneration in zebrafish


Cardiac neural crest cells contribute to important portions of the cardiovascular system including the aorticopulmonary septum and cardiac ganglion. Using replication incompetent avian retroviruses for precise high-resolution lineage analysis, we uncover a previously undescribed neural crest contribution to cardiomyocytes of the ventricles in Gallus gallus, supported by Wnt1-Cre lineage analysis in Mus musculus. To test the intriguing possibility that neural crest cells contribute to heart repair, we examined Danio rerio adult heart regeneration in the neural crest transgenic line, Tg(-4.9sox10:eGFP). Whereas the adult heart has few sox10+ cells in the apex, sox10 and other neural crest regulatory network genes are upregulated in the regenerating myocardium after resection. The results suggest that neural crest cells contribute to many cardiovascular structures including cardiomyocytes across vertebrates and to the regenerating heart of teleost fish. Thus, understanding molecular mechanisms that control the normal development of the neural crest into cardiomyocytes and reactivation of the neural crest program upon regeneration may open potential therapeutic approaches to repair heart damage in amniotes.

Additional Information

© 2019, Tang et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. Publication history: Received: April 25, 2019; Accepted: August 8, 2019; Accepted Manuscript published: August 8, 2019 (version 1); Version of Record published: September 3, 2019 (version 2). We would like to thank Drs. Xia Han and Yang Chai at University of Southern California, Center for Craniofacial Molecular Biology for being extremely supportive and kindly providing Wnt1-Cre; ZsGreenfl/fl cardiac tissue. Many thanks to Dr. Jeffrey Bush at University of California, San Francisco who generously sent us Wnt1-Cre2+; R26mTmG mouse embryos. We appreciate the help from Drs. Ann M Cavanaugh and Jau-Nian Chen at Department of Molecular, Cell and Developmental biology, University of California, Los Angeles in sharing Tg (NC: mCherry) transgenic fish line for Sox10:GAL4-UAS-Cre;ubi:Switch. We would also like to acknowledge the Caltech Millard and Muriel Jacobs Genetics and Genomics Laboratory, in particular, Igor Antoshechkin for sequencing of our RNAseq libraries. We thank Rochelle Diamond and Diana Perez of the the Caltech Flow Cytometry Cell Sorting Facility for cell sorting assistance. We thank David Mayorga and Ryan Fraser of the Beckman Institute Zebrafish Facility for help with zebrafish husbandry and Joanne Tan-Cabugo and Constanza Gonzalez for technical assistance, and Beckman Institute Biological Imaging Facility for equipment. This work is supported by NIHR01DE027568 and NIHRO1HL14058 to MEB and a Helen Hay Whitney Post-doctoral Fellowship to MLM. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Competing interests: Marianne E Bronner: Senior editor, eLife. The other authors declare that no competing interests exist. Author contributions: Weiyi Tang, Conceptualization, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing—original draft, Writing—review and editing, Conceived the project, performed virus preparation, lineage analysis in chick and mouse, immunohistochemistry, quantification, and wrote the manuscript; Megan L Martik, Conceptualization, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing—original draft, Writing—review and editing, Conceived the project, performed the heart regeneration experiments and RNAseq, and wrote the manuscript; Yuwei Li, Formal analysis, Validation, Visualization, Methodology, Writing— original draft, Writing—review and editing, Performed molecular cloning for virus preparation, provided consultation for the manuscript; Marianne E Bronner, Conceptualization, Resources, Supervision, Funding acquisition, Investigation, Writing—original draft, Project administration, Writing—review and editing, Conceived the project, assisted with lineage analysis in chick, and wrote the manuscript. Ethics: Animal experimentation: Adult zebrafish were maintained in the Beckman Institute Zebrafish Facility at Caltech, and all animal and embryo work were completed in compliance with California Institute of Technology Institutional Animal Care and Use Committee (IACUC) protocol 1764. Senior and Reviewing Editor: Didier Y Stainier, Max Planck Institute for Heart and Lung Research, Germany. Data availability: All data is available in the main text, the supplementary materials. Databases have been deposited to NCBI (BioProject # PRJNA526570).

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Published - elife-47929-v2.pdf

Accepted Version - elife-47929-v1.pdf


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August 19, 2023
October 18, 2023