The anatomy of cardiac looping: A step towards the understanding of the morphogenesis of several forms of congenital cardiac malformations

Abstract

The early embryonic heart of vertebrates is a simple tubular pump. During the early phases of its development, the initially straight embryonic heart tube becomes transformed into a helically wound loop that is normally seen with a counterclockwise winding. This process is named cardiac looping. Such looping not only establishes the basic type of topological left-right asymmetry of the ventricular chambers but, additionally, is also said to bring the segments of the heart tube and the developing great vessels into an approximation of their definitive topographical relationships. Cardiac looping is, therefore, regarded as the key process in cardiac morphogenesis and pathologists have speculated since the beginning of the 20th century that several forms of congenital cardiac malformations (e.g., with mirror-imaged arrangement of the ventricular chambers) might result from disturbances in looping morphogenesis. In this article a review is given on (1) differences in the usage of the term cardiac looping; (2) our current knowledge of the dynamically changing anatomy of the looping embryonic heart; and (3) our current knowledge of the role of looping anomalies in the morphogenesis of congenital cardiac malformations.

Endocardial Notch Signaling in Cardiac Development and Disease

“…29 The crescent fuses at the midline forming a primitive heart tube consisting of an inner endocardial layer and an outer myocardial layer separated by an extracellular matrix termed cardiac jelly (Figure 2A and 2B). The heart tube grows at both ends by addition of SHF progenitors into its anterior (arterial) and posterior (venous) poles and simultaneously undergoes rightward looping morphogenesis 30 ( Figure 2C and 2D), changing the initial anterior-posterior polarity into right-left patterning. The FHF will give rise to the left ventricle (LV) and other parts of the heart except the OFT, whereas the SHF gives rise to the OFT myocardium and other parts of the heart except for the LV ( Figure 2C and 2D).…”

The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis

“…Even subtle perturbations in cardiac architecture can lead to congenital heart defects and, in the most extreme forms, to embryonic lethality (Manner, 2009). Despite the obvious clinical implications, little progress has been made in defining the genetic pathways that drive cardiac morphogenesis.…”

“…This tube then undergoes the concurrent morphogenetic events of looping and chamber ballooning to give rise to the mature organ (Manner, 2009). During looping, the heart tube bends away from the body in a process associated with larger, more elongated cells on the convex side versus smaller, more rounded cells on the concave side (Manasek et al, 1972;Soufan et al, 2006;Taber, 2006).…”

How to Make a Heart Valve: From Embryonic Development to Bioengineering of Living Valve Substitutes

“…The heart tube is derived from the first heart field (FHF) of the splanchic mesoderm and contributes cardiac precursors to the atria, atrioventricular canal (AVC), and left ventricle (Buckingham et al 2005). At E9.0, the tubular heart bends right-ward to reorient its original anterior portion along the left -right axis of the embryo and, by doing so, brings the atrial region into a position posterior to the common ventricle (Manner 2009). Concomitantly, the heart expands and elongates at both poles by the addition of progenitor cells coming from a second pool of pharyngeal mesoderm cells called the second heart field (SHF) (Kelly and Buckingham 2002;Dyer and Kirby 2009).…”