Genes required for normal neuronal morphology in Caenorhabditis elegans

Abstract

png-1 encodes the Caenorhabditis elegans homolog of Peptide: N-glycanase, a highly conserved cytosolic enzyme that cleaves N-glycans from misfolded glycoproteins. png-1 was found to regulate several aspects of neuronal morphology including axon branching. In this study, we show that mutations in the NDR kinase pathway genes sax-1 and sax-2 result in png-1 like phenotypes, including excessive branching and ectopic neurites. Furthermore, we found that png-1; sax-1; and png-1; sax-2 double mutants display enhanced defects compared to single mutants, suggesting that png-1 and sax-1/sax-2 act in parallel pathways to restrict axon and branch overgrowth. These interactions suggested a sax-1 enhancer screen as a means to identify additional genes in the png-1 pathway as enhancer mutants should phenocopy png-1 and enhance sax-1 branching defects. This approach recovered at least three sax-1 enhancers ( sens) that act like png-1 to limit axon growth and branching. The identification of these genes should provide new insight into how PNG-1 regulates neuronal morphology.