Genetically identical animals under the same environmental conditions still show strong variability in their behavior, but the source of this variability is unknown. Every neuron expresses hundreds of genes that are essential for its neuronal functioning, such as receptors for sensing and ion-channels. Gene expression is an inherently stochastic process, and hence variability in gene expression of neuron-specific genes could be an important origin of variability in behavior. To address this question, we quantify variability in gene expression in neurons of the nematode C. elegans. We focus on the well-characterized ASE neurons, which are responsible for salt sensing. The transcription factor
che-1 controls ASE neuron specification and maintenance, by inducing hundreds of ASE-specific genes. Crucially,
che-1 also upregulates its own expression, acting as a genetic switch. Hence, variability in
che-1 levels could lead to coordinated variability in targets, and it could as well impact the state of the genetic switch. To measure variability in expression of
che-1 and its targets, we use single molecule FISH to count individual mRNA molecules in the ASE neurons. So far, we have found significant variability in expression of
che-1 and several target genes involved in salt sensing behavior; the ion-channels
tax-2 and
tax-4, and the receptor-type guanylate cyclase
gcy-22 and
gcy-14. Surprisingly, we found that
che-1,
tax-2 and
tax-4 are expressed in very low levels in young worms, ~6 mRNAs per cell. We used stochastic modelling to show that such low levels of
che-1 drastically impact the ability to control expression of itself and its targets, raising the question how
che-1 is still capable of inducing the expression of all target genes and what this implicates for the fluctuations on protein level. Finally, we observed a strong bimodal expression of
gcy-22 in a number of cells around the pharynx, including neuronal support cells. We are currently examining whether this stochastic
gcy-22 expression impacts behavior.