Discoidin domain receptors guide axons along longitudinal tracts in C. elegans

Discoidin domain receptors are a family of receptor tyrosine kinases activated by collagens. Here we characterize the role of the two discoidin domain receptors, ddr-1 and ddr-2, of the nematode C. elegans during nervous system development. ddr-2 mutant animals exhibit axon guidance defects in major longitudinal tracts most prominently in the ventral nerve cord. ddr-1 mutants show no significant phenotype on their own but significantly enhance guidance defects of ddr-2 in double mutants. ddr-1 and ddr-2 GFP-reporter constructs are expressed in neurons with axons in all affected nerve tracts. DDR-1 and DDR-2 GFP fusion proteins localize to axons. DDR-2 is required cell-autonomously in the PVPR neuron for the guidance of the PVPR pioneer axon, which establishes the left ventral nerve cord tract and serves as substrate for later outgrowing follower axons. Our results provide the first insight on discoidin domain receptor function in invertebrates and establish a novel role for discoidin domain receptors in axon navigation and axon tract formation.

► We characterize the role of discoidin domain receptors during neural development.
► ddr-2 mutants exhibit guidance defects in longitudinal axon tracts of C. elegans.
► ddr-1 mutants show no phenotype on their own but act synergistically with ddr-2.
► ddr-1 and ddr-2 are expressed in all affected axon tracts and localize to axons.
► DDR-2 is required cell-autonomously in the ventral nerve cord pioneer neuron PVPR.