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ABSTRACT The heart integrates diverse cell lineages into a functional unit, including the pericardium, a mesothelial sac that supports heart movement, homeostasis, and immune responses. However, despite its critical roles, the developmental origins of the pericardium remain uncertain due to disparate models. Here, using live imaging, lineage tracking, and single-cell transcriptomics in zebrafish, we find the pericardium forms within the lateral plate mesoderm from dedicated anterior mesothelial progenitors and distinct from the classic heart field. Imaging of transgenic reporters in zebrafish documents lateral plate mesoderm cells that emerge lateral of the classic heart field and among a continuous mesothelial progenitor field. Single-cell transcriptomics and trajectories ofhand2-expressing lateral plate mesoderm reveal distinct populations of mesothelial and cardiac precursors, including pericardial precursors that are distinct from the cardiomyocyte lineage. The mesothelial gene expression signature is conserved in mammals and carries over to postnatal development. Light sheet-based live-imaging and machine learning-supported cell tracking documents that during heart tube formation, pericardial precursors that reside at the anterior edge of the heart field migrate anteriorly and medially before fusing, enclosing the embryonic heart to form a single pericardial cavity. Pericardium formation proceeds even upon genetic disruption of heart tube formation, uncoupling the two structures. Canonical Wnt/β-catenin signaling modulates pericardial cell number, resulting in a stretched pericardial epithelium with reduced cell number upon canonical Wnt inhibition. We connect the pathological expression of secreted Wnt antagonists of the SFRP family found in pediatric dilated cardiomyopathy to increased pericardial stiffness: sFRP1 in the presence of increased catecholamines causes cardiomyocyte stiffness in neonatal rats as measured by atomic force microscopy. Altogether, our data integrate pericardium formation as an independent process into heart morphogenesis and connect disrupted pericardial tissue properties such as pericardial stiffness to pediatric cardiomyopathies.
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This content will become publicly available on November 15, 2026
The ratio of Wnt signaling activity to Sox2 transcription factor levels predicts neuromesodermal fate potential
ABSTRACT Neuromesodermal progenitors (NMPs) are a vertebrate cell type that contribute descendants to both the spinal cord and the mesoderm. The undifferentiated bipotential NMP state is maintained when both Wnt signaling is active and Sox2 is present. We used transgenic zebrafish reporter lines to live-image both Wnt activity and Sox2 levels in NMPs and observed a unique cellular ratio in NMPs compared to NMP-derived mesoderm or neural tissue. We used this unique signature to identify the previously unknown anatomical position of a progenitor population that gives rise to midline tissues of the floor plate of the spinal cord and the mesodermal notochord. Thus, quantification of the active Wnt signaling to Sox2 ratio can be used to predict and identify cells with neuromesodermal potential. We also developed the auxin-inducible 2 degron system for use in zebrafish to test the temporal role that Sox2 plays during midline formation. We found that ectopic Sox2 in the presence of Wnt activity holds cells in the undifferentiated floor plate/notochord progenitor state, and that degradation of the ectopic Sox2 is required for cells to adopt a notochord fate.
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- Award ID(s):
- 2028424
- PAR ID:
- 10652258
- Publisher / Repository:
- Company of Biologists
- Date Published:
- Journal Name:
- Development
- Volume:
- 152
- Issue:
- 22
- ISSN:
- 0950-1991
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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