Although His in 1881 and Patten in 1922 suggested that cervical flexio
n could play an important role in normal cardiac morphogenesis, until
recently this hypothesis has been largely neglected. The purpose of th
is report is to present data indicating that prevention of cervical fl
exion leads to double outlet right ventricle (DORV), which is unrelate
d to any affect on neural crest cell migration. At stage 11-12, suture
material was inserted into the neural tube to prevent cervical flexio
n. Six out of 22 experimental embryos survived until stage 38 and 5 ou
t of 6 had DORV. Neither abnormalities of the aortico-pulmonary septum
nor interruption of the aortic arch were observed at dissection. Hemo
dynamic studies performed at stage 18 revealed distinctive characteris
tics that are inconsistent with hemodynamic studies previously reporte
d 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 immunohistoche
mical studies suggest that insertion of suture material into the neura
l tube at stage 11-12 does not jeopardize neural crest migration. We p
ropose that reduction in cervical flexion increases the distance betwe
en the future aorta and the left ventricle, which prevents the transit
ion of intracardiac flow pattern from a serial circulation to a parall
el one, leaving persistence of a ''double outlet'' from the right vent
ricle. (C) 1996 Wiley-Liss, Inc.