REGULATED EXPRESSION OF CHONDROITIN SULFATES AT SITES OF EPITHELIAL-MESENCHYMAL INTERACTION - SPATIOTEMPORAL PATTERNING IDENTIFIED WITH ANTI-CHONDROITIN SULFATE MONOCLONAL-ANTIBODIES

Chondroitin sulfate proteoglycans, cell surface and extracellular matr ix molecules in both neural and non-neural tissues, are highly regulat ed during normal development. Entire proteoglycan molecules may be eit her up-regulated or down-regulated, or only the chondroitin sulfate gl ycosaminoglycan portions of these molecules may be modified. Subtle ch anges in the chemistries of chondroitin sulfate chains can now be iden tified through the use of a panel of anti-chondroitin sulfate monoclon al antibodies. Each of these antibodies recognizes specific chemical s tructures which are non-randomly dispersed along the lengths of chondr oitin sulfate chains. The location of individual epitopes within defin ed domains in these chains is demonstrated through controlled treatmen ts of aggrecan with chondroitinase ABC, whereby portions of these chai ns are removed from the non-reducing terminal ends and where the remai nder of the chains remains covalently attached to the core protein. In these situations, some epitopes, such as those recognized by antibodi es CS-56 and 6C3, can be removed without loss of other epitopes, such as that recognized by antibody 4C3. The independent expression of indi vidual epitopes is demonstrated by immunocytochemical analyses of deve loping skin appendages in embryonic chicks and fetal humans. These are sites where highly patterned morphogenetic movements result from epit helial-mesenchymal interactions. In both chicks and humans, some epito pes are constitutively expressed while others are strictly regulated i n the mesenchymal portions of the developing skin appendages. These da ta strongly suggest that chondroitin sulfate proteoglycans, including their chondroitin sulfate chains, have important roles in regulating t hese epithelial-mesenchymal interactions. Furthermore, these data unde rscore the significance of the aforementioned observation that individ ual epitopes are located in specific domains within chondroitin sulfat e chains. The highly organized expression of chondroitin sulfate prote oglycans in the development of the central nervous system strongly arg ues for a similar role for these molecules in the organs that comprise this system. Copyright (C) 1996.