Examination of tissue specific SAGE libraries revealed a number of putative receptors enriched in neuronal libraries. Available mutants for previously uncharacterized receptors were tested for axon guidance defects which led to the identification of the worm homologs for the mammalian receptor protein-tyrosine kinases (RTKs) DDR1/2 as being involved in ventral cord axon guidance. Forty receptor protein-tyrosine kinases (RTKs) with 11 subfamilies have been identified in the C. elegans genome. Of these RTKs, two discoidin domain receptor genes (C25F6.4 =
ddr-1 and F11D5.3 =
ddr-2) encode homologues of the human discoidin receptors DDR1 and DDR2. Discoidin domain receptors consist of a N-terminal discoidin domain (defined by a 160 amino acid-long homology region), a transmembrane region, an extended juxtamembrane region and a C-terminal intercellular catalytic tyrosine kinase domain. In mammalians various types of collagens have been identified as ligands for the human discoidin domain receptors. To examine the expression of
ddr-1 and
ddr-2, GFP reporter strains were obtained (for
ddr-2) or generated (for
ddr-1). Both genes show expression in subsets of neurons as well as various non-neuronal tissues.
ddr-1::gfp was found in sensory neurons, motoneurons and the HSN, but also in intestine, muscle, pharynx, hyperdermis and gonad.
ddr-2::gfp is expressed in various neurons in head, ventral cord and tail as well as in the intestine, anal depressor muscle, reproductive system and vulval muscle. Putative null alleles for both genes are available from the C. elegans knock-out consortium. A pan-neuronal marker revealed ventral cord cross-over defects in both
ddr-1 and
ddr-2 mutants, which could be identified as PVP/PVQ guidance defects using cell-type specific markers. Currently, we use genetic interaction studies with known axon guidance pathway and ECM components to connect
ddr-1/2 with known pathways and to test the possibility that ECM components like collagens (e.g.
cle-1) might be ligands for these receptors in C. elegans as well. Acknowledgement: The
ddr-2 (BC10719) expression strain was generated by the Genome Expression Project, funded by Genome BC, Genome Canada and CHIR. The
ddr-1 and
ddr-2 alleles were provided by the C. elegans Gene Knockout Projects at OMRF and at NBRP. .