INTEGRATED INTERACTIONS BETWEEN CHONDROITIN SULFATE PROTEOGLYCANS ANDWEAK DC-ELECTRIC-FIELDS REGULATE NERVE GROWTH CONE GUIDANCE IN-VITRO

During development and regenerative growth, neuronal pathways are defi ned in part by several endogenous cues that collectively determine dir ected growth, The interactions between such cues largely are unknown, To address potential interactions, me have examined in vitro the combi ned effect on nerve growth of two endogenous growth cone guidance cues : chondroitin sulphate proteoglycans and weak dc electric fields, Addi tion to the culture medium of a chondroitin 6-sulphate/keratan sulphat e containing PG (BNC-PG) markedly enhanced the cathodal re-orientation of embryonic Xenopus neurites in an electric field, whereas a proteog lycan containing chondroitin 4-sulphate (RC-PG) was inhibitory, These effects of BNC-PG and RC-PG mere reproduced by their chondroitin sulph ate glycosaminoglycan side chains alone, Chondroitin 6-sulphate or cho ndroitin 4-sulphate, respectively, enhanced and inhibited cathodally-d irected nerve re-orientation, This was dependent on the integrity of t he glycosaminoglycan chain structure; when digested into their disacch aride subunits both molecules became inactive, Keratan sulphate, a min or component of BNC-PG, was found to be inhibitory, whereas dermatan s ulphate, an epimer of chondroitin 4-sulphate, had no effect, We conclu de that in vitro specific interactions between these two nerve guidanc e cues do occur and that the specificity of the response is critically dependent on the charge pattern of the proteoglycans chondroitin sulp hate side chains, The expression of a host of proteoglycans with diffe ring glycosaminoglycan side chains varies in both time and place in th e developing nervous system, thus the scope is vast for spatial and te mporal modulation of nerve guidance by interacting cues.