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

Abstract

The nudF and nudC genes of the fungus Aspergillus nidulans encode proteins that are members of two evolutionarily conserved families. In A. nidulans these proteins mediate nuclear migration along the hyphae. The human ortholog of nudF is Lis1, a gene essential for neuronal migration in the developing cerebral cortex. The mammalian ortholog of nudC encodes a protein that interacts with Lis1. We have identified orthologs of nudC and Lis1 from the nematode Caenorhabditis elegans. Heterologous expression of the C. elegans nudC ortholog, nud-1, complements the A. nidulans nudC3 mutant, demonstrating evolutionary conservation of function. A C. elegans nud-1::GFP fusion produces sustained fluorescence in sensory neurons and embryos, and transient fluorescence in the gonad, gut, vulva, ventral cord, and hypodermal seam cells. Fusion of GFP to C. elegans lis-1 revealed expression in all major neuronal processes of the animal as well as the multinucleate spermathecal valves 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 similar to those reported for dynein/dynactin depletion. These results demonstrate that the LIS-1/NUDC-like proteins of C. elegans represent a link between nuclear positioning, cell division, and neuronal function.

Disrupted-in-Schizophrenia 1–mediated axon guidance involves TRIO-RAC-PAK small GTPase pathway signaling

“…1F). RNAi of lis-1 caused embryonic lethality as previously reported (12). However, some escapers that had milder RNAi effects showed significant suppression of the guidance defect (Fig.…”

“…Among these genes, homologs of two well-known mDISC1-interacting genes, pde-4 and lis-1, are present in the C. elegans motor neurons (12) (Fig. S2).…”

Point Mutations in the Stem Region and the Fourth AAA Domain of Cytoplasmic Dynein Heavy Chain Partially Suppress the Phenotype of NUDF/LIS1 Loss in Aspergillus nidulans

“…The connection between LIS1 homologs and cytoplasmic dynein was first made in the filamentous fungus Aspergillus nidulans and the budding yeast Saccharomyces cerevisiae by genetic studies (Xiang et al 1995a;Geiser et al 1997). Further studies have demonstrated that LIS1 and its homologs in higher eukaryotic systems are also involved in cytoplasmic dynein function, and physical interactions between LIS1 and dynein/dynactin have been shown (Liu et al 2000;Sasaki et al 2000;Dawe et al 2001;Tai et al 2002;reviewed by Wynshaw-Boris and Gambello 2001;Gupta et al 2002;Tsai and Gleeson 2005;Vallee and Tsai 2006). Recently, purified LIS1 has been shown to enhance the microtubule-stimulated ATPase activity of the dynein motor (Mesngon et al 2006).…”

Inactivation of a Testis-specific Lis1 Transcript in Mice Prevents Spermatid Differentiation and Causes Male Infertility

“…Whether the apparently different biochemical interactions of Lis1 are functionally related remains to be seen. Proteins homologous to vertebrate Lis1 have been identified in several organisms, including Saccharomyces cerevisiae (29), Aspergillus nidulans (30), Caenorhabditis elegans (31), and Drosophila (32). In yeast and A. nidulans Lis1 homologues play a role in dynein-mediated nuclear migration (30,(33)(34)(35).…”

“…In the mouse, Lis1 also interacts with the nuclear migration proteins NUDC (36) and mNudE-L (37) suggesting a similar role. Abrogation of lis-1 in C. elegans results in embryonic lethality, sterility, altered vulval morphology, uncoordinated movement, and nuclear positioning defects during early embryonic cell divisions (31). Lis1 in Drosophila is also essential for normal development (32).…”