BRAIN AGGRECAN

During development, the extracellular matrix (ECM) is a complex dynami c structure whose components and organization help to establish the re quisite position and state of differentiation. Until recently, the lar ge chondroitin sulfate proteoglycan, aggrecan, has been localized pred ominantly to skeletal tissue and considered a hallmark of cartilage di fferentiation. We have identified the presence of aggrecan in two othe r highly differentiated systems, brain and notochord, with clearly dis tinct expression patterns. In chick cartilage, aggrecan starts to be e xpressed at embryonic day 5 in limb rudiments, continues through the e ntire period of chondrocyte development, and remains a biochemical mar ker of the cartilage phenotype thereafter. In brain, aggrecan has a ve ry low level of expression beginning at day 7, increases up to day 13, markedly decreases after day 16, and is not expressed posthatching. T his pattern coincides with migration and establishment of neuronal nuc lei in the chick telencephalon and has been proposed to be a component of the migration arrest mechanism. In very primitive embryos, aggreca n is detected as early as stage 16 in the notochord, long before chond rogenesis occurs, is then expressed up to day 5 and decreases thereaft er. The expression of aggrecan occurs during the time of active neural crest migration and through the onset of sclerotomal differentiation, and correlates with the notochord's ability to inhibit neural crest c ell migration. Animal models defective in aggrecan biosynthesis have b een invaluable in delineating these functions. In addition we have cha racterized these proteoglycans by chemical, biosynthetic, and molecula r analyses. Although significant post-translational differences distin guish the cell-specific aggrecan species, their core proteins are the products of a single gene. Our findings of the expression of the same gene (aggrecan) in multiple ontogenously unrelated differentiating tis sue systems and at different times over the developmental life of an o rganism provide an elegant model system to study the regulation and in terplay in expression of that gene, as well as the effect of alteratio ns in that single gene simultaneously in several developing programs.