Cervical flexion: Its contribution to normal and abnormal cardiac morphogenesis

Although His in 1881 and Patten in 1922 suggested that cervical flexion could play an important role in normal cardiac morphogenesis, until recently this hypothesis has been largely neglected. The purpose of this report is to present data indicating that prevention of cervical flexion leads to double outlet right ventricle (DORV), which is unrelated to any affect on neural crest cell migration. At stage 11-12, suture material was inserted into the neural tube to prevent cervical flexion. Six out of 22 experimental embryos survived until stage 38 and 5 out of 6 had DORV. Neither abnormalities of the aortico-pulmonary septum nor interruption of the aortic arch were observed at dissection. Hemodynamic studies performed at stage 18 revealed distinctive characteristics that are inconsistent with hemodynamic studies previously reported following neural crest ablation. With respect to immunohistochemical studies using neural crest associated antigen HNK-1 antibody, normal migration of neural crest cells was noted in the outflow tract in the experimental embryos at stage 22. These hemodynamic and immunohistochemical studies suggest that insertion of suture material into the neural tube at stage 11-12 does not jeopardize neural crest migration. We propose that reduction in cervical flexion increases the distance between the future aorta and the left ventricle, which prevents the transition of intracardiac flow pattern from a serial circulation to a parallel one, leaving persistence of a 'double outlet' from the right ventricle.