Chu DS et al. (2013) Adv Exp Med Biol "Spermatogenesis."

Chu DS, Shakes DC

[Adv Exp Med Biol, 2013]

During spermatogenesis, pluripotent germ cells differentiate to become efficient delivery vehicles to the oocyte of paternal DNA. Though male and female germ cells both undergo meiosis to produce haploid complements of DNA, at the same time they also each undergo distinct differentiation processes that result in either sperm or oocytes. This review will discuss our current understanding of mechanisms of sperm formation and differentiation in Caenorhabditis elegans gained from studies that employ a combination of molecular, transcriptomic, and cell biological approaches. Many of these processes also occur during spermatogenesis in other organisms but with differences in timing, molecular machinery, and morphology. In C. elegans, sperm differentiation is implemented by varied modes of gene regulation, including the genomic organization of genes important for sperm formation, the generation of sperm-specific small RNAs, and the interplay of specific transcriptional activators. As sperm formation progresses, chromatin is -systematically remodeled to allow first for the implementation of differentiation programs, then for sperm-specific DNA packaging required for transit of paternal genetic and epigenetic information. Sperm also exhibit distinctive features of -meiotic progression, including the formation of a unique karyosome state and the centrosomal-based segregation of chromosomes during symmetric meiotic -divisions. Sperm-specific organelles are also assembled and remodeled as cells complete -meiosis and individualize in preparation for activation, morphogenesis, and the acquisition of motility. Finally, in addition to DNA, sperm contribute specific cellular factors that contribute to successful embryogenesis.

Wu TF et al. (2010) Syst Biol Reprod Med "Elucidating gene regulatory mechanisms for sperm function through the integration of classical and systems approaches in C. elegans."

Chu DS, Shakes DC, Wu TF, Nera B

[Syst Biol Reprod Med, 2010]

From worms to mammals, successful spermatogenesis depends on a gene expression profile that balances activating and repressive mechanisms. Besides developmental control of specific spermatogenic genes, male fertility requires temporal shifts in global gene expression and dramatic changes in chromatin structure and condensation. Recent studies are beginning to elucidate the molecular processes that both drive these temporal changes in gene expression and underlie fertility. In this review, we provide an overview of relevant C. elegans studies that have laid the groundwork for modern approaches. Next, we highlight recent studies that investigate how gene expression in C. elegans is modulated during spermatogenesis. These studies use large-scale genomic profiling in combination with bioinformatics, genetics, biochemistry, and in vitro methods to target specific stages or processes during sperm formation. Such studies are beginning to elucidate the multiple layers of gene regulation required during spermatogenesis, i.e., transcriptional, post-transcriptional, and epigenetic. Moreover, knowledge of how C. elegans coordinately regulates gene expression during spermatogenesis promises to provide key insights into parallel processes in mammals that are vital for fertility.

Sharp PA (1999) Genes Dev "RNAi and double-strand RNA."

Sharp PA

[Genes Dev, 1999]

Double-strand RNA (dsRNA) is a signal for gene-specific silencing of expression in a number of organisms. This phenomenon was demonstrated recently in Caenorhabditis elegans when dsRNA was injected into the worm and the corresponding gene products disappeared from both the somatic cells of the organism as well as in its F1 progeny. This RNA interference, RNAi, has been generalized to many genes in C. elegans. ds-RNA can also suppress expression of specific genes in plants, a component of the phenomenon called cosuppression. Two recent reports document dsRNA-mediated interference with expression of specific genes in other organisms. Double-strand RNA produced gene-specific phenotypes in Trypanosoma brucei and, very recently, dsRNA-mediated interference was demonstrated in Drosophila. Thus, the RNAi phenomenon is likely to be a general mechanism for gene regulation and may be critical for many developmental and antiviral processes.

Au C et al. (2008) Neurotoxicology "Manganese transport in eukaryotes: the role of DMT1."

Au C, Benedetto A, Aschner M

[Neurotoxicology, 2008]

Manganese (Mn) is a transition metal that is essential for normal cell growth and development, but is toxic at high concentrations. While Mn deficiency is uncommon in humans, Mn toxicity is known to be readily prevalent due to occupational overexposure in miners, smelters and possibly welders. Excessive exposure to Mn can cause Parkinson''s disease-like syndrome; patients typically exhibit extrapyramidal symptoms that include tremor, rigidity and hypokinesia [Calne DB, Chu NS, Huang CC, Lu CS, Olanow W. Manganism and idiopathic parkinsonism: similarities and differences. Neurology 1994;44(9):1583-6; Dobson AW, Erikson KM, Aschner M. Manganese neurotoxicity. Ann NY Acad Sci 2004;1012:115-28]. Mn-induced motor neuron diseases have been the subjects of numerous studies; however, this review is not intended to discuss its neurotoxic potential or its role in the etiology of motor neuron disorders. Rather, it will focus on Mn uptake and transport via the orthologues of the divalent metal transporter (DMT1) and its possible implications to Mn toxicity in various categories of eukaryotic systems, such as in vitro cell lines, in vivo rodents, the fruitfly, Drosophila melanogaster, the honeybee, Apis mellifera L., the nematode, Caenorhabditis elegans and the baker''s yeast, Saccharomyces cerevisiae.