DEVELOPMENTAL EXPRESSION OF PERLECAN DURING MURINE EMBRYOGENESIS

Perlecan is a modular heparan sulfate proteoglycan that is an intrinsi c constituent of all basement membranes and extracellular matrices. Be cause of its strategic position and unique structure, perlecan has bee n implicated in modulating the activity of various growth factors requ ired for normal development and tissue homeostasis. To gain insights i nto the potential function of perlecan in vivo, we examined the spatio temporal distribution of its mRNA and protein core during murine embry ogenesis. We utilized a new affinity-purified antibody that recognizes specifically the protein core of perlecan together with an in situ RT -PCR approach to perform a systematic analysis of perlecan expression and deposition during murine ontogeny. Perlecan appeared early (E10.5) in tissues of vasculogenesis including heart, pericardium, and major blood vessels. Its early expression coincided with the development of the cardiovascular system. Subsequently (E11-13), the greatest deposit ion of perlecan occurred within the developing cartilage, especially t he cartilage undergoing endochondral ossification, where it remained e levated throughout all the developmental stages, and up to adulthood. Interestingly, the mRNA levels of perlecan were always higher in all t he vascularized tissues, principally within endothelial cells, while c hondrocytes displayed relatively low mRNA levels. This suggests a high er biosynthesis and turnover rates in the blood vessels vis-a-vis thos e of cartilaginous and other mesenchymal tissues. During later stages of development (E13-17.5) perlecan mRNA levels progressively increased and its expression correlated with the onset of tissue differentiatio n of various parenchymal organs including the developing kidneys, lung s, liver, spleen, and gastrointestinal tract. The central nervous syst em showed no perlecan expression with the exception of the calvaria an d choroid plexus. Collectively, the results indicate that perlecan may play crucial roles not only in vasculogenesis but also in the maturat ion and maintenance of differentiated tissues, including cartilage. (C ) 1997 Wiley-Liss, Inc.