Pubs before 2007

Food can be hazardous, either through toxicity or through bacterial infections that follow the ingestion of a tainted food source. Because learning about food quality enhances survival, one of the most robust forms of olfactory learning is conditioned avoidance of tastes associated with visceral malaise. The nematode Caenorhabditis elegans feeds on bacteria but is susceptible to infection by pathogenic bacteria in its natural environment. Here we show that C. elegans modifies its olfactory preferences after exposure to pathogenic bacteria, avoiding odours from the pathogen and increasing its attraction to odours from familiar nonpathogenic bacteria. Particular bacteria elicit specific changes in olfactory preferences that are suggestive of associative learning. Exposure to pathogenic bacteria increases serotonin in ADF chemosensory neurons by transcriptional and post-transcriptional mechanisms. Serotonin functions through MOD-1, a serotonin-gated chloride channel expressed in sensory interneurons, to promote aversive learning. An increase in serotonin may represent the negative reinforcing stimulus in pathogenic infection.

The extent of gene regulation in cell differentiation is poorly understood. We previously used saturation mutagenesis to identify 18 genes that are needed for the development and function of a single type of sensory neuron--the touch receptor neuron for gentle touch in Caenorhabditis elegans. One of these genes, mec-3, encodes a transcription factor that controls touch receptor differentiation. By culturing and isolating wild-type and mec-3 mutant cells from embryos and applying their amplified RNA to DNA microarrays, here we have identified genes that are known to be expressed in touch receptors, a previously uncloned gene (mec-17) that is needed for maintaining touch receptor differentiation, and more than 50 previously unknown mec-3-dependent genes. These genes are randomly distributed in the genome and under-represented both for genes that are co-expressed in operons and for multiple members of gene families. Using regions 5' of the start codon of the first 20 genes, we have also identified an over-represented heptanucleotide, AATGCAT, that is needed for the expression of touch receptor genes.

We have used representational difference analysis (RDA) applied to cDNA to isolate transcripts regulated by MEC-3, a transcription factor needed for the differentiation of the six touch receptor neurons in Caenorhabditis elegans. Six percent of 595 cDNAs isolated by cDNA RDA were mec-3-dependent. These cDNAs represented mRNA from two previously known genes, mec-18 and mec-7, and one new gene, mtd-1 (mec-three-dependent). mtd-1 encodes a novel transmembrane protein that is exclusively expressed in the six touch cells throughout development. mtd-1 loss results in a subtle defect in the touch receptor neurons. Neither mtd-1 RNAi nor a putative mtd-1 loss-of-function mutation resulted in touch insensitivity, but both enhanced the touch insensitivity of mec-6(u247), a temperature sensitive allele, at the permissive temperature.