In contrast to mammals, zebrafish regenerate heart injuries via proliferation of cardiomyocytes located near the wound border. To identify regulators of cardiomyocyte proliferation, we used spatially resolved RNA sequencing (tomo-seq) and generated a high-resolution genome-wide atlas of gene expression in the regenerating zebrafish heart. Interestingly, we identified two wound border zones with distinct expression profiles, including the re-expression of embryonic cardiac genes and targets of bone morphogenetic protein (BMP) signaling. Endogenous BMP signaling has been reported to be detrimental to mammalian cardiac repair. In contrast, we find that genetic or chemical inhibition of BMP signaling in zebrafish reduces cardiomyocyte dedifferentiation and proliferation, ultimately compromising myocardial regeneration, while bmp2b overexpression is sufficient to enhance it. Our results provide a resource for further studies on the molecular regulation of cardiac regeneration and reveal intriguing differential cellular responses of cardiomyocytes to a conserved signaling pathway in regenerative versus non-regenerative hearts.
Sensitive nonradioactive detection of mRNA in tissue sections: novel application of the whole-mount in situ hybridization protocol
Bone morphogenetic protein-2 inhibits serum deprivation-induced apoptosis of neonatal cardiac myocytes through activation of the Smad1 pathway
Germ-line transmission of a myocardium-specific GFP transgene reveals critical regulatory elements in the cardiac myosin light chain 2 promoter of zebrafish
BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3
Tol2 transposon-mediated enhancer trap to identify developmentally regulated zebrafish genes in vivo
A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration
The Wilms tumor genes wt1a and wt1b control different steps during formation of the zebrafish pronephros
Bone morphogenetic protein 4 mediates myocardial ischemic injury through JNK-dependent signaling pathway
Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration
Regeneration of cryoinjury induced necrotic heart lesions in zebrafish is associated with epicardial activation and cardiomyocyte proliferation
The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion
Bmp and nodal independently regulate lefty1 expression to maintain unilateral nodal activity during left-right axis specification in zebrafish
Bone morphogenetic protein-4 mediates cardiac hypertrophy, apoptosis, and fibrosis in experimentally pathological cardiac hypertrophy
Tbx20 promotes cardiomyocyte proliferation and persistence of fetal characteristics in adult mouse hearts
Translational profiling of cardiomyocytes identifies an early Jak1/Stat3 injury response required for zebrafish heart regeneration
A transgenic mouse model for the simultaneous monitoring of ANF and BNP gene activity during heart development and disease
Bone morphogenetic protein-2 antagonizes bone morphogenetic protein-4 induced cardiomyocyte hypertrophy and apoptosis
Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish
Collagen XII Contributes to Epicardial and Connective Tissues in the Zebrafish Heart during Ontogenesis and Regeneration
Bone morphogenetic protein signaling governs biliary-driven liver regeneration in zebrafish through tbx2b and id2a
Opposite effects of Activin type 2 receptor ligands on cardiomyocyte proliferation during development and repair
Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate
Characterization of zebrafish (Danio rerio) muscle ankyrin repeat proteins reveals their conserved response to endurance exercise
Chromatin Conformation Links Putative Enhancers in Intracranial Aneurysm-Associated Regions to Potential Candidate Genes
A Systematic Exposition of Methods used for Quantification of Heart Regeneration after Apex Resection in Zebrafish.
Epicardial TGFβ and BMP Signaling in Cardiac Regeneration: What Lesson Can We Learn from the Developing Heart?
AP-1 Contributes to Chromatin Accessibility to Promote Sarcomere Disassembly and Cardiomyocyte Protrusion During Zebrafish Heart Regeneration.
Midkine-a functions as a universal regulator of proliferation during epimorphic regeneration in adult zebrafish.
Loss of the Polycomb group protein Rnf2 results in derepression of tbx-transcription factors and defects in embryonic and cardiac development
The Gridlock transcriptional repressor impedes vertebrate heart regeneration by restricting expression of lysine methyltransferase.
Zebrafish as a Smart Model to Understand Regeneration After Heart Injury: How Fish Could Help Humans
Tbx20 Induction Promotes Zebrafish Heart Regeneration by Inducing Cardiomyocyte Dedifferentiation and Endocardial Expansion
Concise Review: Hematopoietic Stem Cell Origins: Lessons from Embryogenesis for Improving Regenerative Medicine
Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration
Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart.
Runx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regeneration.
Gene expression imputation and cell type deconvolution in human brain with spatiotemporal precision and its implications for brain-related disorders
Reactive oxygen species during heart regeneration in zebrafish: Lessons for future clinical therapies.
Is zebrafish heart regeneration "complete"? Lineage-restricted cardiomyocytes proliferate to pre-injury numbers but some fail to differentiate in fibrotic hearts.
Sexual Dimorphism through the Lens of Genome Manipulation, Forward Genetics, and Spatiotemporal Sequencing.
Induction of Wnt signaling antagonists and p21-activated kinase enhances cardiomyocyte proliferation during zebrafish heart regeneration.
In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration.
A Heterozygous Mutation in Cardiac Troponin T Promotes Ca2+ Dysregulation and Adult Cardiomyopathy in Zebrafish.
Hemodynamic Forces Regulate Cardiac Regeneration-Responsive Enhancer Activity during Ventricle Regeneration.
Cardiac regeneration enables the repair of irreversibly damaged heart tissue using cutting-edge science, including stem cell and cell-free therapy. Discover the latest research on cardiac regeneration here.