Downstream Targets of let-60 Ras in Caenorhabditis elegans

Abstract

In Caenorhabditis elegans, let-60 Ras controls many cellular processes, such as differentiation of vulval epithelial cells, function of chemosensory neurons, and meiotic progression in the germ line. Although much is known about the let-60 Ras signaling pathway, relatively little is understood about the target genes induced by let-60 Ras signaling that carry out terminal effector functions leading to morphological change. We have used DNA microarrays to identify 708 genes that change expression in response to activated let-60 Ras.

Global analysis of dauer gene expression inCaenorhabditis elegans

“…For these 2430 genes, we employed a two-way mixed-model ANOVA as implemented by SAS to identify 1984 genes with different kinetics between the dauer exit and L1 starvation timecourses (P<0.05) (Romagnolo et al, 2002). We used a self-organizing map to cluster the 1984 genes of the dauer-specific data set into 45 nodes using 15 million iterations with Cluster software (Eisen et al, 1998).…”

Developmental and Biological Insights Obtained from Gene Expression Profiling of the Nematode Caenorhabditis Elegans

“…In this respect, the administration of exogenous compounds to C. elegans is more simplistic since worms can be soaked in drug solution, or grown on agar plates with a defined drug concentration. Gene expression studies made with disease models have revealed different transcription profiles for certain genes [28,30]. This is the kind of data that should be further investigated in order to discover new therapeutic targets.…”

“…An example of such an approach was taken by Romagnolo and colleagues [30], who produced transgenic overexpressing animals with constitutively active let-60(G12V) using a heat shock promoter to control transgene expression. LET-60 is the worm ortholog of Ras which is an important molecular switch that controls many developmental processes including tumour growth and neuronal differentiation.…”

“…At the opposite end of the spectrum, over expressing transgenic C. elegans animals have the limitation that the gene is constitutively expressed. Studies have addressed this by driving expression using conditional promoters [28,30].…”

A biochemist’s guide to Caenorhabditis elegans

“…Among many examples, microarrays have been used to examine C. elegans gene expression at various stages of development [64][65][66], in both sexes to identify male and female germline-specific transcripts [67], in animals that differ in the number of a particular structure such as male tail rays [68], in animals that have been differentially treated with ethanol [69], and in animals that have activated or overexpressed transcription factors to identify downstream target genes [70,71]. In addition to isolating RNA from a staged population of animals, techniques have been developed for isolating RNA from single tissues or cell types.…”