Spatio-temporal specificity in trans-activation of the perlecan gene during development is key to the maturation of basement membranes and thus to the complete separation of epithelia from endothelia and stroma. A thorough study of perlecan expression during chick embryo development has shown that perlecan is present at the morula stage and for the rest of development, although expression can be transient and precisely timed in certain tissue predecessors. In the rat embryo, perlecan expression has been shown to increase in vascular smooth muscle cells (VSMCs) post e19 in fetal development. This correlates perfectly with the ceasing of proliferation of VSMCs at e18 and a change in their phenotype. The theory put forward in this study is that perlecan plays an anti-proliferative role for VSMCs once a certain developmental point is reached, much like confluence-dependent expression of perlecan in culture. These findings were corroborated by similar results from studies of rat pulmonary artery and lung epithelia. These tissues also were found to begin perlecan production once cell division had ceased, around fetal day 19.