Focal adhesions are essential to drive zebrafish heart valve morphogenesis

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  • 飯田, 敦夫
    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research
  • 瀬原, 淳子
    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research
  • Fukuda, Ryuichi
    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research
  • Tsedeke, Ayele Taddese
    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research
  • Jiménez-Amilburu, Vanesa
    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research
  • Ramadass, Radhan
    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research
  • Iida, Atsuo
    Institute for Frontier Life and Medical Sciences, Kyoto University
  • Sehara-Fujisawa, Atsuko
    Institute for Frontier Life and Medical Sciences, Kyoto University
  • Stainier, Didier Y.R.
    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research

抄録

Elucidating the morphogenetic events that shape vertebrate heart valves, complex structures that prevent retrograde blood flow, is critical to understanding valvular development and aberrations. Here, we used the zebrafish atrioventricular (AV) valve to investigate these events in real time and at single-cell resolution. We report the initial events of collective migration of AV endocardial cells (ECs) into the extracellular matrix (ECM), and their subsequent rearrangements to form the leaflets. We functionally characterize integrin-based focal adhesions (FAs), critical mediators of cell–ECM interactions, during valve morphogenesis. Using transgenes to block FA signaling specifically in AV ECs as well as loss-of-function approaches, we show that FA signaling mediated by Integrin α5β1 and Talin1 promotes AV EC migration and overall shaping of the valve leaflets. Altogether, our investigation reveals the critical processes driving cardiac valve morphogenesis in vivo and establishes the zebrafish AV valve as a vertebrate model to study FA-regulated tissue morphogenesis.

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