Previous studies have demonstrated that the primordial pulmonary veins orig
inate as an outgrowth of the atrial cells and anastomosis with the pulmonar
y venous plexus, As a consequence of this embryologic origin the tunica med
ia of these vessels is composed of cardiac cells that express atrial specif
ic markers (Lyons et al, [1990] J Cell Biol 111:2427-2436; Jones et al, [19
94] Dev Dyn 200:117-128), We used transgenic mice for the cardiac troponin
I (cTNI) gene and smooth muscle (SM) myosin heavy chain as differentiation
markers, to analyze how cardiac and SM cells contribute to the formation an
d structural remodeling of the pulmonary veins during development, We show
here that the tunica media of the adult mouse pulmonary veins contains an o
uter layer of cardiac cells and an intermediate SM cell compartment lining
down on the inner endothelium, This structural organization is well express
ed in the intrapulmonary veins from the beginning of vasculogenesis, with c
ardiac cells accumulating over preexisting roots of endothelial and SM cell
s and extending to the third bifurcation of the pulmonary branches without
reaching the more distal tips of the vessels, On the other hand, SM cells,
which are widely distributed in the intrapulmonary veins from the embryonic
stage E16, accumulate also in the extrapulmonary branches and reach the po
sterior wall of the left atrium, including the orifices of the pulmonary ve
ins, This event takes place around birth when the pulmonary blood flow star
ts to function properly, A model for the development of the pulmonary veins
is presented, based upon our analysis. (C) 2000 Wiley-Liss, Inc.