The UNC-83/UNC-84 LINC members are required for body wall muscle nuclei positioning in C. elegans

From a mutagenesis screen in the nematode C. elegans we isolated the mutant bar18, showing an accumulation of muscle cell nuclei around the posterior pharyngeal bulb of the worm. Quantification of the overall amount of body wall muscle nuclei, based on the muscle-specific reporter myo-3p::gfp::NLS, revealed that the number of nuclei in bar18 mutants is unchanged compared to WT worms. The accumulation of muscle nuclei around the posterior pharyngeal bulb is due to a positioning defect, which can be precisely quantified by subdividing the worm into head, neck, and posterior body segments. Whole-genome sequencing revealed that bar18 animals carry a mutation in the KASH-domain gene unc-83 causing a premature STOP. An additional unc-83 mutant allele recapitulates the phenotype, as does a mutant allele of UNC-84, a SUN-domain containing protein that interacts with UNC-83. UNC-83 and UNC-84 belong to a Linker of Nucleoskeleton and Cytoskeletonnuclear (LINC) complex that bridges the nuclear lamina with the cytoskeleton. SUN and KASH domain proteins are conserved in mammals and mutations in the corresponding genes have been linked to cancer, autism, muscular dystrophy and other diseases. Additionally, LINC complexes that function in nuclear migration have also been identified in mammals. We were able to rescue the unc-83 mutant phenotype by expressing the WT gene under a muscle-specific (myo-3p) promoter, demonstrating that the effect is cell autonomous. Mutations in either unc-83 or unc-84 have previously been linked to nuclear migration defects in P cells, intestinal cells and hyp7 hypodermal precursors but not in muscles. Whether the mis-positioning of muscle nuclei is due to migration or anchoring defects still needs to be determined.