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Asymmetric Involution of the Myocardial Field Drives Heart Tube Formation in Zebrafish

From the Max Delbrück Center for Molecular Medicine (S.R., C.O., S.A.-S.), Berlin; and Department of Biology (S.R.), University of Freiburg, Germany.

Correspondence to Salim Abdelilah-Seyfried, Max Delbrück Center for Molecular Medicine, Robert-Rössle Str. 10, 13125 Berlin, Germany. E-mail salim{at}mdc-berlin.de

Many vertebrate organs are derived from monolayered epithelia that undergo morphogenesis to acquire their shape. Whereas asymmetric left/right gene expression within the zebrafish heart field has been well documented, little is known about the tissue movements and cellular changes underlying early cardiac morphogenesis. Here, we demonstrate that asymmetric involution of the myocardium of the right-posterior heart field generates the ventral floor, whereas the noninvoluting left heart field gives rise to the dorsal roof of the primary heart tube. During heart tube formation, asymmetric left/right gene expression within the myocardium correlates with asymmetric tissue morphogenesis. Disruption of left/right gene expression causes randomized myocardial tissue involution. Time-lapse analysis combined with genetic analyses reveals that motility of the myocardial epithelium is a tissue migration process. Our results demonstrate that asymmetric morphogenetic movements of the 2 bilateral myocardial cell populations generate different dorsoventral regions of the zebrafish heart tube. Failure to generate a heart tube does not affect the acquisition of atrial versus ventricular cardiac cell shapes. Therefore, establishment of basic cardiac cell shapes precedes cardiac function. Together, these results provide the framework for the integration of single cell behaviors during the formation of the vertebrate primary heart tube.

Key Words: heart tube • cell polarity • protein kinase C iota • left–right asymmetry • southpaw • nagie oko

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