The NC1/endostatin domain of Caenorhabditis elegans type XVIII collagen affects cell migration and axon guidance

Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a poten t antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue , cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. D eletion of the cle-1 NC1 domain results in viable fertile animals that disp lay multiple cell migration and axon guidance defects. Particular defects c an be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does n ot rescue but dominantly causes cell and axon migration defects that phenoc opy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain reg ulates cell and axon migrations in C. elegans.