Jonathan H Freedman et al. (2005) International Worm Meeting "Changes in Gene Expression Associated with Exposure to Environmental Toxicants"

Michelle Chen, Yuxia Cui, Jonathan H Freedman, Sean Coughlan, Windy A Boyd

[International Worm Meeting, 2005]

When organisms are exposed to toxicants, they defend themselves against intracellular damage by activating the transcription of genes that encode proteins that defend the host, repair the damage, or remove/metabolize the toxicant. Changes in expression of these proteins following toxicant exposure is referred to as the stress-response. Since many of these stress-response proteins and the signal transduction cascades that regulate the stress-response are evolutionarily conserved, we hypothesize that exposure to environmental toxicants modulates the transcription of an evolutionarily conserved set of genes from yeast to mammals. To investigate this hypothesis we are comparing the expression profiles from yeast and C. elegans that were exposed to archetypical toxicants. In the present study we examined the responses of wild type C. elegans to the carcinogenic transition metal cadmium and the DNA alkylating agent N-methyl-N-nitro-nitrosoguanidine (MNNG). Toxicological studies for both cadmium and MNNG were performed to determined exposure times and toxicant concentrations. Bases on the effects of these agents on feeding, reproduction, and growth, nematodes were exposed to 0.1 mM cadmium and 4 ppm MNNG for 4h and 24h. Transcriptomes for cadmium- and MNNG-exposed nematodes were obtained by Agilents C. elegans oligonucleotide microarray analysis. This microarray contains ~20,000 targets, based on sequence information obtained from the WS105 release of WormPep, the C. elegans EST database and Genbank. Current analysis indicates that 47 genes are differential expressed after 4 h cadmium exposure, and 115 genes are differential expressed after a 24 h exposure (fold change&#8805;2, p<0/01). Over 400 genes were differentially expressed following MNNG exposure. Subsequently the functions of these genes will be identified and compared to identify conserved and divergent Gene Ontologys (GO), pathways (KEGG) and interactomes nodes (Cytoscape) among the gene whose levels of expression affected by cadmium and MNNG. The result will help us to discover not only expression profiles associated with specific toxicants, but also common stress-response genes regulated by different environmental toxicants. Moreover, this result will be incorporated into a larger study to compare the expression profiles from four species (yeast, C. elegans, zebrafish embryos and mice) exposed to different classes of toxicants in order to define evolutionarily conserved regulatory pathways that control the stress response.

Prasad BC et al. (1997) International C. elegans Meeting "THE C. ELEGANS unc-3 GENE ENCODES A HOMOLOGUE OF THE O/E FAMILY OF MAMMALIAN TRANSCRIPTION FACTORS"

Prasad BC, Reed RR, Seydoux GC

[International C. elegans Meeting, 1997]

The expression of specialized signal transduction components in mammalian olfactory neurons is thought to be regulated by the O/E (Olf-1/EBF) family of transcription factors. The O/E proteins are expressed in cells of the olfactory neuronal lineage throughout development, and are also expressed transiently in neurons in the developing nervous system during embryogenesis. We have identified a C. elegans homologue of the mammalian O/E proteins, which displays greater than 80% similarity over 350 amino acids. The CeO/E cDNA maps to cosmid F42D1, previously shown to encode unc-3(1). We demonstrate that CeO/E is the product of the unc-3 gene, mutations in which cause defects in the axonal outgrowth of motor neurons as well as defects in dauer formation, a process requiring chemosensory input. Like its mammalian homologues, CeO/E is expressed in certain chemosensory neurons (ASI amphid neurons) throughout development, and is also expressed transiently in developing motor neurons when these cells undergo axonal outgrowth. Currently, we are defining the DNA sequence binding specificity of the CeO/E protein. These observations suggest that the O/E family of transcription factors play a central and evolutionarily conserved role in the expression of proteins essential for axonal pathfinding and neuronal differentiation. (1) Sean Eddy, WBG 12(5):86 (February 1, 1993)