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Keywords:

  • cardiac looping;
  • simulation model;
  • handedness;
  • left-right asymmetry

Abstract

The internal organs of vertebrates show specific anatomical left-right asymmetries. The embryonic heart is the first organ to develop such asymmetries during a process called dextro-looping. Thereby the initially straight heart tube curves toward its original ventral side and the resulting bend becomes displaced toward the right side of the embryo. Abnormal displacement of the heart loop toward the left is rare and is called levo-looping. Descriptive studies have shown that the lateralization of the heart loop is driven by rotation around its dorsal mesocardium. However, nothing was known on the modes of this process. To gain insight into this subject, different modes of rotation were tested in a simulation model for the looping chick embryo heart. The morphological phenotypes obtained in this model were compared with normal and mirror-imaged embryonic hearts. The following observations were made. One, rotation of the heart loop around its dorsal mesocardium has two consequences: first, lateral displacement of its bending portion either toward the right (D-loop) or left (L-loop) side of the embryo, and second, torsion of the cardiac bend into a helical structure that is wound either clockwise (right-handed helix) or counterclockwise (left-handed helix). The normal loop presents as a D-loop with left-handed helical winding and its mirror image presents as an L-loop with right-handed helical winding. This conflicts with the use to define D-loops as right- and L-loops as left-handed structures. Two, dextro-looping might be driven almost exclusively by rightward rotation of the arterial pole of the loop. It becomes complemented by leftward rotation of the venous pole during the subsequent phase of looping. An inverse mode of rotation might drive levo-looping. Three, the two different helical configurations of heart loops both can occur as right-sided, median, or left-sided positional variants. When viewed from the front, all right-sided variants appear as D-loops and all left-sided variants appear as L-loops at the end of dextro- or levo-looping. Their true asymmetric phenotypes become fully apparent only after simulation of the subsequent phase of looping. The terms D- and L-loop obviously do not fully define the chirality of heart loops. The chirality of their helical configuration should be defined, too. The implications of these data with respect to molecular and experimental data are discussed. Anat Rec Part A 278A:481–492, 2004. © 2004 Wiley-Liss, Inc.