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Published online 19 March 2001. doi:10.1083/jcb.152.6.1219
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© The Rockefeller University Press, 0021-9525/2001//1219 $5.00
The Journal of Cell Biology, Volume 152, Number 6, , 2001 1219-1232

Original Article

The Nc1/Endostatin Domain of Caenorhabditis elegans Type Xviii Collagen Affects Cell Migration and Axon Guidance



Brian D. Ackleya, Jennifer R. Crewa, Harri Elamaab, Tania Pihlajaniemib, Calvin J. Kuoc, and James M. Kramera

a Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611
b Collagen Research Unit, Biocenter, and Department of Medical Biochemistry, University of Oulu, FIN-90014 Oulu, Finland
c Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115
Department of Cell and Molecular Biology, Northwestern University Medical School, 303 East Chicago Ave., Chicago, IL 60611.(312) 503-7912(312) 503-7644

jkramer{at}nwu.edu

Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent 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. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can 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 not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

Key Words: cell migration • neurogenesis • endostatin • collagen • Caenorhabditis elegans

© 2001 The Rockefeller University Press

Abbreviations used in this paper: dsRNA, double-stranded RNA; ECM, extracellular matrix; EGS, ethylene glycol bis-succinic acid; ES, endostatin; GFP, green fluorescent protein; HSN, hermaphrodite-specific neuron; RNAi, RNA interference; RT, reverse transcription.


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