| The goal of this research was to understand the molecular mechanisms that control germline specification. Towards this end, I have undertaken a molecular analysis of the mes-6 gene, a grandchildless gene identified in the nematode Caenorhabditis elegans. Previous genetic studies have shown that maternally-expressed wild-type mes-6 product is necessary and sufficient for post-embryonic germline development. mes-6 mutants have a maternal-effect sterile phenotype because embryos lacking wild-type mes-6 product develop into adults with few germ cells, and these germ cells do not differentiate into gametes. In order to determine how mes-6 controls germline development, I isolated the gene and examined its protein product.; mes-6 was cloned by a combination of approaches. DNA containing the wild-type version of the mes-6 gene was identified by its ability to rescue the mes-6 mutant phenotype. The smallest rescuing fragment contained a number of transcripts. The mes-6 transcript was identified by antisense inhibition and sequencing DNA from worms bearing mutant alleles. Sequence analysis and database searches revealed that mes-6 encodes a WD-40 repeat protein similar to Drosophila extra sex combs protein, a member of the Polycomb group of genes that are responsible for long-term transcriptional repression. Another mes gene with a similar phenotype, mes-2, has been isolated, and it is similar to Enhancer of zeste, another Polycomb group gene. I propose a model in which the mes genes control germline fate by regulating gene expression in the germline. I also found that mes-6 is in an operon with a homolog of the Saccharomyces cereviseae cyclin kinase subunit, cks-1. |
