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    Tissue-level Mechanisms Driving Cardiac Progenitor and Extracellular Matrix Movements during Early Vertebrate Heart Development

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    Issue Date
    2012-12-31
    Author
    Aleksandrova, Anastasiia
    Publisher
    University of Kansas
    Format
    267 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Anatomy & Cell Biology
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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    Abstract
    Vertebrate cardiogenesis involves heart progenitor cell movements from their initial lateral positions to the embryonic midline, where they assemble into a primitive heart. This early heart tube consists of an outer myocardium, a medial extracellular matrix (ECM), and an endocardial lining. Cardiac morphogenesis in avians and mammals is inseparable from development of the foregut, which provides molecular cues to regulate endocardial and myocardial differentiation from mesodermal progenitors. Concomitantly with the initiation of midline-directed cardiac progenitor movements, foregut endoderm undergoes dramatic folding and elongation. Following their initial assembly, the heart and foregut are transiently connected through a mesentery. Previous research focused on the molecular factors involved in guiding cardiac progenitors to the midline, yet cellular and tissue mechanisms coordinating these movements remain poorly understood. This work investigates movements of all three early heart constituents - the endocardial and myocardial progenitors, and surrounding ECM - in live quail embryos using a combination of time-lapse microscopy, chemical and mechanical perturbations, computational analysis and modeling. By visualizing the tissue environment for cell displacements, we distinguish the active (tissue-independent) movements from those cells undergo in a manner coordinated with the surrounding tissues. First, we analyzed the movements of endocardial progenitors and fluorescently-labeled ECM (fibronectin, fibrillin-2) fibrils. We found the bulk of midline-directed movement of pre-endocardial cells is coordinated with their surrounding ECM. Further, that ECM from extracardiac sources is transferred to and incorporated into the growing heart. By assessing the contributions of active cell motility to the observed midline endocardial displacements we found its role to be secondary to that of convective tissue movement within the anterior embryo. Second, we assessed myocardial progenitor movements relative to fibronectin ECM and endoderm. We discovered that observed antero-medial myocardial displacements are driven by a combination of: 1) medial tissue motion, and 2) anterior movement, accomplished via a coordinated deformation of myocardial progenitors, organized into a continuous epithelial sheet. Finally, we investigated the effects of VEGF overexposure on progenitor movements during early cardiogenesis. We found a dramatic VEGF-induced increase in cardiac inflow region size, which affected the coordinated movements/deformations displayed by myocardial progenitors, and resulted in heart tube elongation defects.
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    http://hdl.handle.net/1808/11448
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    • Dissertations [4475]
    • KU Med Center Dissertations and Theses [464]

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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