To understand how neurons polarize in vivo we studied the morphology of two bipolar motorneurons (VC4 and VC5), which polarize medial-laterally (ML) to innervate the egg-laying system of C elegans. To identify genes responsible for the bipolar ML morphology we performed genetic screens to isolate worms with defective VC4/5 polarity. So far we have isolated mutations in prickle-1 (prickle homolog-1 LGIV, 4 alleles),
vang-1 (Van Gogh homolog-1 LGX, 3 alleles) and
dsh-1 (dishevelled homolog-1 LGII, 1 allele) genes that result in ectopic misdirected axons. VC4 & 5 neurons in
prkl-1,
vang-1 and
dsh-1 mutants extend a third axon in the AP axis rendering neurons with tripolar morphology. Here we report that evolutionary conserved Planar Cell Polarity (PCP) genes
prkl-1,
vang-1 and
dsh-1 mediate the ML orientation of VC4 and VC5 by suppressing ectopic axon outgrowth along the anterior-posterior axis. We explore the biological mechanism underlying the novel role for
prkl-1,
vang-1 and
dsh-1 in the polarity of VC4 and VC5 by performing cell rescue experiments, loss and gain-of-function studies, examining the localization of functional translational fusions and analyzing the expression of transcriptional reporters.