In its function of separating pulmonary and systemic arterial blood flow, t
he ductus arteriosus, which connects both circuits, either closes permanent
ly at a certain stage in development or attains a capacity to close and reo
pen depending on the physiological needs in certain species. In air-breathi
ng vertebrates varying from lungfish to mammals, the ductus arteriosus deri
ves from the sixth pharyngeal arch artery, and in preparation for its speci
fic task, undergoes its own unique differentiation programme, starting earl
y in development. To date, the mechanisms involved in defining this unique
status, as compared to the other great arteries, are unclear. This re-view
clarifies some of the elusiveness of the ductus arteriosus. It includes a c
omparative description of this artery in species exemplifying the different
classes of air-breathing vertebrates, and illustrates similarities and dif
ferences in morphogenesis and closure Mechanisms among the species. It also
deals with possible influences of vascular innervation and with congenital
anomalies in which the ductus arteriosus is involved. New data suggest tha
t HOXB5 expression in the neural crest along the dorsal half of the sixth a
rch artery may be involved in the instigation of ductus arteriosus differen
tiation.