SPATIAL AND TEMPORAL EXPRESSION OF THE 72-KDA TYPE-IV COLLAGENASE (MMP-8) CORRELATES WITH DEVELOPMENT AND DIFFERENTIATION OF VALVES IN THE EMBRYONIC AVIAN HEART

Extracellular proteases may play an important role in the regulation o f cell migration and remodeling of the extracellular matrix during dev elopment, In this study, we have examined the embryonic avian heart fo r the expression of matrix metalloproteases. The 72-kDa type IV collag enase, MMP-2, was detected in extracts of whole hearts and showed a mo dest increase in amount over time, This increase in enzyme activity co rresponded to a small increase in the steady-state level of mRNA for t his enzyme, A more dramatic increase was seen in the amount of the 66- kDa activated form of this enzyme as development progressed, suggestin g that the process of activation, rather than enzyme synthesis, may be the important regulatory step in this system, Coincident with the cha nge in the level of active MMP-2 was a significant increase in the exp ression of the MMP-2 activator, MT-MMP, between stages 12 and 24, The message for MMP-2 was expressed by the endocardium of the cushion tiss ues which was undergoing an epithelial-mesenchymal transition, and by the migrating mesenchymal cells, suggesting a role for this protease i n regulating cell motility and matrix invasion, In older staged hearts , the cells of the differentiating valves expressed high levels of MMP -2 which may be important for the final remodeling events in this regi on. (C) 1997 Wiley-Liss, Inc.