PROLIFERATION AND DIFFERENTIATION OF SMOOTH-MUSCLE CELL PRECURSORS OCCURS SIMULTANEOUSLY DURING THE DEVELOPMENT OF THE VESSEL WALL

Formation of the blood vessel wall depends on the recruitment, prolife ration, and differentiation of smooth muscle cell (SMC) precursors, Th e temporal events associated with the onset of expression of several S MC proteins have been well characterized in mouse and avian species. H owever, the timing of cell proliferation during this process has not b een explored, More importantly, it has not been clear whether commitme nt to the smooth muscle pathway precludes proliferation during develop ment, In the present study, we have determined the kinetics of replica tion in developing chick aortae between days 2.5 and 19 and have corre lated these data with the expression of various SMC differentiation ma rkers, We found that proliferation of aortic SMC precursors occurs in two waves; an early phase of rapid proliferation (15-17%; between days 4 and 12), and a second phase, when replication was reduced to less t han 5% (days 16 to hatching), Proliferation of SMC during the first wa ve occurred concomitantly with the progressive accumulation of SMC con tractile proteins, such as SM alpha-actin, calponin, myosin heavy chai n, and the 1E12 antigen, We also found that the relative proliferation capacity within each compartment of the vessel wall, ie., intima, med ia, and adventitia varies throughout development. Approximately, 55-63 % of all replicating cells were found in the tunica adventitia from da ys 6 to 12, whereas 35% were found in the tunica media (tunica media:a dventitia = 1:2), This ratio was inverted after day 12, when most of t he replicating cells were located in the tunica media (tunica media:ad ventitia = 2:1), In addition, we observed a ventral-to-dorsal gradient in the proliferation of SMC precursors between days 2.5 and 5. The ve ntral-to-dorsal proliferation gradient was similar to the previously d escribed differential expression of two early SMC markers: alpha-actin and the 1E12 antigen. These data support the concept that a polarity exists either in the pool of SMC precursors or, in expression of facto rs that regulate recruitment of presumptive SMC. (C) 1997 Wiley-Liss, Inc.