Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III

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Abstract

Genome sequencing projects generate a wealth of information; however, the ultimate goal of such projects is to accelerate the identification of the biological function of genes. This creates a need for comprehensive studies to fill the gap between sequence and function. Here we report the results of a functional genomic screen to identify genes required for cell division in Caenorhabditis elegans. We inhibited the expression of 96% of the 2,300 predicted open reading frames on chromosome III using RNA-mediated interference (RNAi). By using an in vivo time-lapse differential interference contrast microscopy assay, we identified 133 genes (6%) necessary for distinct cellular processes in early embryos. Our results indicate that these genes represent most of the genes on chromosome III that are required for proper cell division in C. elegans embryos. The complete data set, including sample time-lapse recordings, has been deposited in an open access database. We found that 47% of the genes associated with a differential interference contrast phenotype have clear orthologues in other eukaryotes, indicating that this screen provides putative gene functions for other species as well.

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Figure 1: Single images taken from time-lapse DIC recordings of wild-type (left) and embryos representative of six distinct phenotypic classes (right).
Figure 2: Distribution of predicted proteins according to homology and orthology relationships.

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Acknowledgements

For help in improving the manuscript, we thank A. Desai, A. Ephrussi, S. Grill, M. Labouesse, I. Mattaj and B. Sönnichsen. Work in the Hyman laboratory is supported by the EMBL (European Molecular Biology Laboratory) and the MPI (Max-Planck-Institute). P.G. was supported by a fellowship from the Swiss National Science Foundation. A.C. is supported by the UK Medical Research Council.

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Correspondence to Anthony A. Hyman.

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