Evolutionarily conserved nuclear migration genes required for early embryonic development in Caenorhabditis elegans

The nudF and nudC genes of the fungus Aspergillus nidulans encode proteins that are members of two evolutionarily conserved families. In A. nidulans t hese proteins mediate nuclear migration along the hyphae. The human ortholo g of nudF is Lis1, a gene essential for neuronal migration in the developin g cerebral cortex. The mammalian ortholog of nudC encodes a protein that in teracts with Lis1. We have identified orthologs of nudC and Lis1 from the n ematode Caenorhabditis elegans. Heterologous expression of the C. elegans n udC ortholog, nud-1, complements the A. nidulans nudC3 mutant, demonstratin g evolutionary conservation of function. A C. elegans nud-1::GFP fusion pro duces sustained fluorescence in sensory neurons and embryos, and transient fluorescence in the gonad, gut, vulva, ventral cord, and hypodermal seam ce lls. Fusion of GFP to C. elegans lis-1 revealed expression in all major neu ronal processes of the animal as well as the multinucleate spermathecal val ves and adult seam cells. Phenotypic analysis of either nud-1 and lis-1 by RNA interference yielded similar phenotypes, including embryonic lethality, sterility, altered vulval morphology, and uncoordinated movement. Digital time-lapse video microscopy was used to determine that RNAi-treated embryos exhibited nuclear positioning defects in early embryonic cell division sim ilar to those reported for dynein/dynactin depletion. These results demonst rate that the LIS-1/NUDC-like proteins of C. elegans represent a link betwe en nuclear positioning, cell division, and neuronal function.