Spatial and temporal expression of the 72-kDa type IV collagenase (MMP-2) correlates with development and differentiation of valves in the embryonic avian heart.

Extracellular proteases may play an important role in the regulation of cell migration and remodeling of the extracellular matrix during development. In this study, we have examined the embryonic avian heart for the expression of matrix metalloproteases. The 72-kDa type IV collagenase, MMP-2, was detected in extracts of whole hearts and showed a modest increase in amount over time. This increase in enzyme activity corresponded to a small increase in the steady-state level of mRNA for this enzyme. A more dramatic increase was seen in the amount of the 66-kDa activated form of this enzyme as development progressed, suggesting that the process of activation, rather than enzyme synthesis, may be the important regulatory step in this system. Coincident with the change in the level of active MMP-2 was a significant increase in the expression 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 tissues which was undergoing an epithelial-mesenchymal transition, and by the migrating mesenchymal cells, suggesting a role for this protease in 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 region.