A review concerning some embryogenetic aspects of the cardiac outflow tract is presented. Two main topics are discussed: the truncal septation and the secondary heart field. In the context of the septation of the truncus arteriosus, the development of the arterial valves is largely discussed, particularly in reference to the sinuses of Valsalva. Emphasis is also given to the fate of the external myocardial wall of the truncus arteriosus, as this primordial myocardial surface disappears later in the development. Molecular genetics data concerning Sox4 and NF-Atc transcription factors are correlated in the present review with rare forms of truncus malformations encountered in human pathology. The roles exerted by the secondary heart field and the neural crest on the development and growth of the conotruncal musculature are largely discussed. Reported experimental ablations of both secondary heart field and neural crest, showed conotruncal defects such as persistent truncus arteriosus, tetralogy of Fallot, and double-outlet right ventricle, which were considered as the result of a short outflow tract causing, ultimately, a lack of conotruncal rotation. In this regard, some morphologic correlations are carried out, in the present review, between these experimental animal models and human malformations, and it is thought that this sort of conotruncal defects cannot be explained always in terms of conotruncal hypoplasia. Finally, influence of Pitx2c, a left-right laterality signaling gene, on the modulation of the conotruncal rotation, as most recently reported, is emphasized in terms of very likely multifactorial contributions in the embryogenesis of the conotruncal region of the heart.
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