Rotation and Asymmetric Development of the Zebrafish Heart Requires Directed Migration of Cardiac Progenitor Cells

• Published in: Developmental cell Vol. 14; no. 2; pp. 287 - 297
• Main Authors: Smith, Kelly A., Chocron, Sonja, von der Hardt, Sophia, de Pater, Emma, Soufan, Alexander, Bussmann, Jeroen, Schulte-Merker, Stefan, Hammerschmidt, Matthias, Bakkers, Jeroen
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 01.02.2008; Cell Press
• Subjects: Animals; Biological and medical sciences; Body Patterning - drug effects; Bone Morphogenetic Proteins - pharmacology; Cell differentiation, maturation, development, hematopoiesis; Cell Lineage - drug effects; Cell Movement - drug effects; Cell physiology; DEVBIO; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - drug effects; Fundamental and applied biological sciences. Psychology; Glucuronosyltransferase - metabolism; Heart - drug effects; Heart - embryology; Humans; Hyaluronan Synthases; Left-Right Determination Factors; Mesoderm - cytology; Mesoderm - drug effects; Molecular and cellular biology; Mutation - genetics; Myocardium - cytology; Rotation; Signal Transduction - drug effects; Smad Proteins - metabolism; Stem Cells - cytology; Stem Cells - drug effects; Transforming Growth Factor beta - metabolism; Zebrafish - embryology; Zebrafish Proteins - metabolism; DEVBIO; Heart; Vertebrata; Brachydanio rerio; Pisces; Migration; Development; Circulatory system; Progenitor cell
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2007.11.015

We have used high-resolution 4D imaging of cardiac progenitor cells (CPCs) in zebrafish to investigate the earliest left-right asymmetric movements during cardiac morphogenesis. Differential migratory behavior within the heart field was observed, resulting in a rotation of the heart tube. The leftward displacement and rotation of the tube requires hyaluronan synthase 2 expression within the CPCs. Furthermore, by reducing or ectopically activating BMP signaling or by implantation of BMP beads we could demonstrate that BMP signaling, which is asymmetrically activated in the lateral plate mesoderm and regulated by early left-right signals, is required to direct CPC migration and cardiac rotation. Together, these results support a model in which CPCs migrate toward a BMP source during development of the linear heart tube, providing a mechanism by which the left-right axis drives asymmetric development of the vertebrate heart.