Formal genesis of the outflow tracts of the heart revisited: Previous works in the light of recent observations

Abstract

The formal genesis of the great arteries continues to be controversial due to the lack of consensus of septation of the developing outflow tract. In order to make it clear how the great arteries are generated, we have re-examined our previous papers which emphasized the formation of the aorta and pulmonary trunk, concept of the aorticopulmonary septum, formation of the leaflets of semilunar valves, morphogenesis of the crista supraventricularis, programmed cell death and rotation of the outflow tract. In the present paper, we compare outcomes gained from the re-examination of our previous papers with prevalent interpretations of the arterial trunk. We obtained conclusions as follows: (i) The elongation of the fourth and sixth aortic arch arteries, which sprout from the wall of the aortic sac at the expense of the distal truncus, contributes to the formation of the aorta and pulmonary trunk; (ii) Smooth muscle cells of the tunica media of the arterial trunks do not arise from the transformation of the myocardial cells of the truncus wall (not 'arterialization'); (iii) Truncus swellings are divided into two parts: distal and proximal. The former contributes to the separation of the orifices of arterial trunks ('aorticopulmonary septum'). The latter contributes to the formation of the leaflets of the semilunar valves of the aorta and pulmonary trunk; (iv) The origin of the myocardial cells of the crista supraventricularis is a wall of the conus originated from secondary/anterior heart fields; and (v) There has been no acceptable proof that rotation and counterclockwise rotation are involved.

Ectopic retinoic acid signaling affects outflow tract cushion development through suppression of the myocardial Tbx2-Tgfβ2 pathway

“…Taken together, these observations strongly suggest that the hypoplastic proximal cushion ridges in association with shortening and rotational defects of the OFT are the part of etiology leading TGA morphology in RA-treated embryos. It remains to be investigated how RA affects the morphogenesis of the OFT, including cushion formation, septation, elongation/rotation and retraction of the conotruncus (Okamoto et al, 2010).…”

Partitioning the heart: mechanisms of cardiac septation and valve development

“…4C, Fig. 6A,B) (Restivo et al, 2006;Okamoto et al, 2010). Conal cushions, capable of supporting EMT of the endocardium, probably have major contributions to the aforementioned valve leaflets, of which the mesenchymal tissues largely come from the endocardium (de Lange et al, 2004).…”

Hemorrhagic infiltration of the aortopulmonary adventitia: A complication of acute aortic dissection

“…Then, the truncus arteriosus and the cranial end of the bulbus cordis become gradually separated by the aorticopulmonary septum. This septum is composed of two ridge-like projections derived from cardiac neural crest cells, which later fuse together to create a continuous bridge and form the separate lumens of the aorta and main pulmonary artery [13,14]. As can be seen in Fig.…”