Live-imaging reveals Coordinated Cell Migration and Cardiac Fate Determination during Mammalian Gastrulation

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Abstract

Heart development involves the specification of cardiac progenitors at distinct stages and locations. Using live-imaging of mouse embryos between gastrulation and heart tube formation, we tracked individual mesodermal cells and reconstructed their lineage trees for up to five cell divisions. We found independent unipotent progenitors emerging at specific times, contributing exclusively to either left ventricle/atrioventricular canal (LV/AVC) or atrial myocytes. LV/AVC progenitors differentiated early to form the cardiac crescent, while atrial progenitors later generated the heart tube’s inflow tract during morphogenesis. We also identified short-lived bipotent progenitors with broad potential, illustrating early developmental plasticity. Sister cells from bipotent progenitors displayed greater dispersion and more diverse migratory trajectories within the anterior mesoderm than those from unipotent progenitors. Bipotent progenitors contributing to extraembryonic mesoderm (ExEm) exhibited the fastest and most dispersed migrations, whereas those giving rise to endocardial, LV/AVC, and pericardial cells showed a more gradual divergence, with late-stage behavioural shifts: endocardial cells increased in speed, while pericardial cells slowed relative to LV/AVC cells. Together the data reveal the regulation of individual cell directionality and cardiac fate allocation within the seemingly unorganised migratory pattern of mesoderm cells.

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  1. Note: This response was posted by the corresponding author to Review Commons. The content has not been altered except for formatting.

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    Reviewer #1

    Evidence, reproducibility and clarity

    The manuscript describes the tracking of individual mesoderm cells through live imaging. Through a combination of reporters including a novel cardiomyocyte reporter and a combined nuclear GFP-inducible Cre reporter under the dependance of the Brachyury promoter, the authors label mesoderm cells at different stages of gastrulation then perform long term (>30h) live imaging of late gastrulation embryo up to the cardiac crescent and heart tube stages. They use elaborate analysis tools as well as manual tracking to reconstruct cells' trajectory, lineage trees, and various behavioral traits.

    The study is …

  2. Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

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    Referee #3

    Evidence, reproducibility and clarity

    In their manuscript, Abukar et al. investigate the origins and migratory behaviors of cardiac progenitor cells, in mice, from gastrulation to early heart tube formation. They use sophisticated live imaging to tracks individual mesodermal cells, reconstructing their lineage and fate over several generations. The findings reveal distinct unipotent progenitors that contribute exclusively to specific cardiac regions, such as the left ventricle/atrioventricular canal (LV/AVC) or atrial cardiomyocytes. LV/AVC progenitors differentiate early, forming the cardiac crescent, while atrial progenitors differentiate later, contributing to the …

  3. Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

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    Referee #2

    Evidence, reproducibility and clarity

    The authors perform an elegant "tour de force" lineage relationships during mouse heart development. They perform long-term live imaging and single-cell tracking in mouse embryos from early gastrulation to stages of heart tube formation. They then track the progeny of individual cells and reconstruct the lineage tree of tracked cells. They analyze how their migratory paths of cells correlate with cell fate in the heart. Altogether, the manuscript presents a highly detailed live-imaging lineage tracing study of a subset of cells in the cardiac crescent in mouse. This presents a nice contribution to the literature, but would be …

  4. Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

    Learn more at Review Commons


    Referee #1

    Evidence, reproducibility and clarity

    The manuscript describes the tracking of individual mesoderm cells through live imaging. Through a combination of reporters including a novel cardiomyocyte reporter and a combined nuclear GFP-inducible Cre reporter under the dependance of the Brachyury promoter, the authors label mesoderm cells at different stages of gastrulation then perform long term (>30h) live imaging of late gastrulation embryo up to the cardiac crescent and heart tube stages. They use elaborate analysis tools as well as manual tracking to reconstruct cells' trajectory, lineage trees, and various behavioral traits.

    The study is well designed. Experiments are …